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  • 1. Chen, Lin
    et al.
    Guo, Jiangfeng
    Sharma, Alok
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skaper, Stephen D.
    Huang, Hongyun
    Summary Report of the International Association of Neurorestoratology VII Conference: Regulations, Ethics, Science, and the Need of Patients Care in Neurorestoratology2014In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 13, no 6, 921-925 p.Article in journal (Refereed)
  • 2. Chen, Lin
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Guo, Jiangfeng
    Muresanu, Dafin
    Huang, Hongyun
    Skaper, Stephen
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Conference Report Annual advances in neurorestoratology: a summary of IANR VI and 10th GCNN conference, Bucharest, Romania, April 4-7, 20132013In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 12, no 5, 547-549 p.Article in journal (Refereed)
  • 3. Feng, L.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Tian, Z. R.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanowired Delivery of Mesenchymal Stem Cells (MSCs) Attenuates Pathophysiology of Spinal Cord Injury and Enhances Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor-1 Concentrations in the Plasma and the Spinal Cord2014In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 23, no 6, 769-770 p.Article in journal (Other academic)
  • 4. Feng, L.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Engineered Nanoparticles From Metals (Ag, Cu, Al, 50-60 nm) Aggravate Neuropathic Pain Syndrome and Exacerbate Blood-Spinal Cord Barrier Breakdown, Astrocytic Activation, and Neural Injury: Neuroprotection by Cerebrolysin Treatment2012In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 21, no 4, 777-777 p.Article in journal (Other academic)
  • 5. Feng, Lianyuan
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin Fior
    Moessler, Herbert
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Engineered nanoparticles from metals aggravate spinal cord injury induced neuropathic pain syndrome and exacerbate blood-spinal cord barrier breakdown, astrocytic activation and neural injury: Neuroprotective effects of cerebrolysin2014In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 28, no 5-6, 525-525 p.Article in journal (Other academic)
  • 6. Lafuente, Jose Vicente
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patnaik, Ranjana
    Muresanu, Dafin Fior
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Diabetes Exacerbates Nanoparticles Induced Brain Pathology2012In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 11, no 1, 26-39 p.Article, review/survey (Refereed)
    Abstract [en]

    Long term exposure of nanoparticles e.g., silica dust (SiO2) from desert environments, or engineered nanoparticles from metals viz., Cu, Al or Ag from industry, ammunition, military equipment and related products may lead to adverse effects on mental health. However, it is unclear whether these nanoparticles may further adversely affect human health in cardiovascular or metabolic diseases e.g., hypertension or diabetes. It is quite likely that in diabetes or hypertension where the body immune system is already compromised there will be greater adverse effects following nanoparticles exposure on human health as compared to their exposure to healthy individuals. Previous experiments from our laboratory showed that diabetic or hypertensive animals are more susceptible to heat stress-induced neurotoxicity. Furthermore, traumatic injury to the spinal cord in SiO2 exposed rats resulted in exacerbation of cord pathology. However, whether nanoparticles such as Cu, Ag or SiO2 exposure will lead to enhanced neurotoxicity in diabetic animals are still not well investigated. Previous data from our laboratory showed that Cu or Ag intoxication (50 mg/kg, i.p. per day for 7 days) in streptozotocine induced diabetic rats exhibited enhanced neurotoxicity and exacerbation of sensory, motor and cognitive function as compared to normal animals under identical conditions. Thus the diabetic animals showed exacerbation of regional blood-brain barrier (BBB) disruption, edema formation and cell injuries along with greater reduction in the local cerebral blood flow (CBF) as compared to normal rats. These observations suggest that diabetic animals are more vulnerable to nanoparticles induced brain damage than healthy rats. The possible mechanisms and functional significance of these findings are discussed in this review largely based on our own investigations.

  • 7. Lin, Jiuluan
    et al.
    Zhou, Wenjing
    Zhang, GuangMing
    Zhang, Yuqi
    Sharma, Hari S.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Zuo, Huancong
    Novel Method to Identify the Precentral Gyrus and Its Detailed Functional Distribution in Real Brain Surfaces Using Reconstructed 3D Brain Surface Imaging2015In: JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS, ISSN 2156-7018, Vol. 5, no 2, 216-222 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To study the use of reconstructed 3D brain surface imaging (RBSI) to identify the precentral gyrus and its detailed functional distribution in epileptic patients. Method: A total of 12 refractory epilepsy cases that need intracranial electrode implantation were studied. In these patients, pre-operative magnetic resonance imaging (MRI) and functional MRI (fMRI) were conducted, and a cranial computed tomography (CT) scan was performed after electrode implantation. The RBSI was accomplished using Brain Voyager software based on MRI data, and then the 3D brain surface was integrated with the subdural electrode CT scan. The precentral gyrus was found in the reconstructed brain surface imaging according to their anatomical shape, and then were identified in the surgical field by comparing the exposed gyrus in the RBSI with the help of intraoperative photographs. Results: Total 12 cases of precentral gyrus was found and marked in the RBSI. There were 101 electrodes covering the precentral gyrus and 73 (72%) of them had motor response to electrical stimulation. In the contrast, (the area which is 1 cm ahead of the precentral gyrus), the motor response rate was 13% (17/130) (p < 0.05). During fMRI, 100% of the precentral gyrus and 58% (7/12) of post central gyrus was activated during hand movement. Whereas, no activation of the areas ahead of precentral gyrus was seen showing a significant difference between precentral gyrus and gyrus ahead. Conclusion: Our results demonstrated that using RBSI technique, it is possible to identify the precentral gyrus with precision.

  • 8.
    Menon, P. K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Aguilar, Z. P.
    Wang, Y. A.
    Lafuente, J. V.
    Moessler, H.
    Patnaik, R.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Functionalized Magnetic Iron Oxide Nanoparticles Influence Spinal Cord Trauma-Induced Pathology: Neuroprotective Effects of Cerebrolysin Treatment2013In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, no 5, 909-909 p.Article in journal (Other academic)
  • 9. Menon, Preeti Kumaran
    et al.
    Muresanu, Dafin Fior
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Moessler, Herbert
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cerebrolysin, a Mixture of Neurotrophic Factors Induces Marked Neuroprotection in Spinal Cord Injury Following Intoxication of Engineered Nanoparticles from Metals2012In: CNS & Neurological Disorders - Drug Targets, ISSN 1871-5273, Vol. 11, no 1, 40-49 p.Article, review/survey (Refereed)
    Abstract [en]

    Spinal cord injury (SCI) is the world's most disastrous disease for which there is no effective treatment till today. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum (Al), silver (Ag) and copper (Cu) (50-60 nm) when administered in rats daily for 7 days (50 mg/kg, i.p.) resulted in exacerbation of cord pathology after trauma that correlated well with breakdown of the blood-spinal cord barrier (BSCB) to serum proteins. The entry of plasma proteins into the cord leads to edema formation and neuronal damage. Thus, future drugs should be designed in such a way to be effective even when the SCI is influenced by nanoparticles. Previous research suggests that a suitable combination of neurotrophic factors could induce marked neuroprotection in SCI in normal animals. Thus, we examined the effects of a new drug; cerebrolysin that is a mixture of different neurotrophic factors e.g., brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and other peptide fragments to treat normal or nanoparticle-treated rats after SCI. Our observations showed that cerebrolysin (2.5 ml/kg, i.v.) before SCI resulted in good neuroprotection in normal animals, whereas nanoparticle-treated rats required a higher dose of the drug (5.0 ml/kg, i.v.) to induce comparable neuroprotection in the cord after SCI. Cerebrolysin also reduced spinal cord water content, leakage of plasma proteins and the number of injured neurons. This indicates that cerebrolysin in higher doses could be a good candidate for treating SCI cases following nanoparticle intoxication. The possible mechanisms and functional significance of these findings are discussed in this review.

  • 10. Muresanu, D. F.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patnaik, R.
    Moessler, H.
    Sharma, H. S.
    Blood-Brain Barrier Breakdown, Edema Formation, Nitric Oxide Synthase Upregulation and Brain Pathology in Diabetic and Hypertensive Rats Following Heat Stroke: Neuroprotective Effects of Titanium Nanowired Cerebrolysin2013In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, no 5, 910-911 p.Article in journal (Other academic)
  • 11. Muresanu, D. F.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patnaik, R.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Enhanced Neuroprotection by Nanowired Delivery of Cerebrolysin in Hyperthermia-Induced Brain Damage2012In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 21, no 4, 786-786 p.Article in journal (Other academic)
  • 12.
    Muresanu, D. F.
    et al.
    Univ Med & Pharm, Clin Neurosci.;RoNeuro Inst Neurol Res & Diagnost, Neurol..
    Sharma, Aruna
    Uppsala Univ Hosp, Surg Sci Anesthesiol & Intens Care Med..
    Sharma, Hari Shanker
    Uppsala Univ Hosp, Surg Sci Anesthesiol & Intens Care Med..
    Pathophysiology of high altitude traumatic brain edema: New roles of cererbrolysin and nanomedicine2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, 208-209 p.Article in journal (Other academic)
  • 13. Muresanu, D. F.
    et al.
    Winkler, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nozari, A.
    Menon, P. K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cerebrolysin enhances spinal cord conduction and reduces blood-spinal cord barrier breakdown, oedema formation, immediate early gene expression and cord pathology after injury2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, 798-798 p.Article in journal (Other academic)
  • 14.
    Muresanu, D.
    et al.
    Univ Med & Pharm, Clin Neurosci, Cluj Napoca, Romania..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lafuente, J.
    Univ Basque Country, Neurosci, Bilbao, Spain..
    Patnaik, R.
    Banaras Hindu Univ, IIT, Biomed Engn, Varanasi, Uttar Pradesh, India..
    Tian, Z.
    Univ Arkansas Faytteville, Chem & Biochem, Faytteville, AR USA..
    Ozkizilcik, A. S. Y. A.
    Univ Arkansas Faytteville, Chem & Biochem, Faytteville, AR USA..
    Moessler, H.
    Ever Neuro Pharma, Drug Dev & Discovery, Oberburgau, Austria..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanowired cerebrolysin potentiates mesenchymal stem cells induced neuroprotection and neurorepair following heat stroke2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, 317-317 p., 457Article in journal (Other academic)
  • 15.
    Muresanu, Dafin F.
    et al.
    RoNeuro Inst Neurol Res & Diagnost, Cluj Napoca, Romania.;Univ Med & Pharm Iuliu Haticganu, Dept Clin Neurosci, Cluj Napoca, Romania..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lafuente, Jose V.
    Univ Basque Country, Dept Neurosci, LaNCE, Bilbao, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
    Patnaik, Ranjana
    Banaras Hindu Univ, Sch Biomed Engn, Indian Inst Technol, Dept Biomat, Varanasi 221005, Uttar Pradesh, India..
    Tian, Z. Ryan
    Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA..
    Nyberg, Fred
    Uppsala Univ, Biomed Ctr, Dept Pharmaceut Biosci Biol Res Drug Dependence, Uppsala, Sweden..
    Sharma, Hari S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Basque Country, Dept Neurosci, LaNCE, Bilbao, Spain..
    Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord2015In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 837-845 p.Article in journal (Refereed)
    Abstract [en]

    Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.

  • 16. Muresanu, Dafin F.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patnaik, Ranjana
    Moessler, Herbert
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cerebrolysin restores amino acid neurotransmitters balance in the brain following traumatic head injury: an experimental study in the rat2013In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 45, no 3, 565-565 p.Article in journal (Other academic)
  • 17.
    Muresanu, Dafin F.
    et al.
    Univ Med & Pharm, Dept Neurosci, Cluj Napoca, Romania..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patnaik, Ranjana
    Banaras Hindu Univ, Indian Inst Technol, Varanasi 221005, Uttar Pradesh, India..
    Nozari, Ala
    Harvard Univ, Massachusetts Gen Hosp, Anesthesiol, Boston, MA 02115 USA..
    Tian, Z. Ryan
    Univ Arkansas, Chem & Biochem, Fayetteville, AR 72701 USA..
    Ozkizilcik, Asya
    Univ Arkansas, Chem & Biochem, Fayetteville, AR 72701 USA..
    Moessler, Herbert
    Ever NeuroPharma, Oberburgau, Austria..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Uppsala, Sweden..
    Nanodelivery of cerebrolysin induces profound neuroprotection in heat stroke following chronic hypertension in combination with carbon nanoparticles induced exacerbation of brain damage2016In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 30, no 5-6, 506-507 p.Article in journal (Other academic)
  • 18. Muresanu, Dafin F.
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tian, Z. Ryan
    Smith, Mark A.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanowired Drug Delivery of Antioxidant Compound H-290/51 Enhances Neuroprotection in Hyperthermia-Induced Neurotoxicity2012In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 11, no 1, 50-64 p.Article, review/survey (Refereed)
    Abstract [en]

    Nanoparticles from the environment or through industrial sources can induce profound alterations in human health, often leading to brain dysfunction. However, it is still unclear whether nanoparticle intoxication could also alter the physiological or pathological responses of additional brain injury, stress response or disease processes. Military personals engaged in combat or peacekeeping operations are often exposed to nanoparticles from various environmental sources, e.g., Ag, Cu, Si, C, Al. In addition, these military personals are often exposed to high environmental heat, or gun and missle explosion injury leading to head or spinal trauma. Thus it is likely that additional CNS injury or stress-induced pathophysiological processes are influenced by nanoparticle intoxication. In this situation, when a combination of nanoparticles and central nervous system (CNS) injury or stress exist together, drug therapy needed to correct these anomalies may not work as effectively as in normal situation. Previous studies from our laboratory show that nanoparticle-intoxicated animals when subjected to hyperthermia resulted in exacerbation of brain pathology. In these animals, antioxidant compounds, e.g., H-290/51 that inhibits free radical formation and induces marked neuroprotection in normal rats after heat stress, failed to protect brain damage when a combination of nanoparticles and heat exposure was used. However, nanowired H-290/51 resulted in better neuroprotection in nanoparticles intoxicated animals after heat stress. Interestingly, high doses of the normal compound induced some neuroprotection in these nanoparticle-treated, heat-stressed rats. These observations suggest that a combination of nanoparticles and heat stress is dangerous and in such situations modification of drug dosage is needed to achieve comparable neuroprotection. In this review possible mechanisms of nanoparticle-induced exacerbation of heat induced neurotoxicity and brain protection achieved by nanowired drug delivery is discussed that is largely based on our own investigations.

  • 19. Pandey, Anand Kumar
    et al.
    Patnaik, Ranjana
    Muresanu, Dafin F
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Quercetin in hypoxia-induced oxidative stress: novel target for neuroprotection2012In: New Perspectives of Central Nervous System Injury and Neuroprotection / [ed] Sharma, HS, Elsevier, 2012, 107-146 p.Chapter in book (Refereed)
    Abstract [en]

    Oxidative stress in the central nervous system is one of the key players for neurodegeneration. Thus, antioxidants could play important roles in treating several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and aging-related brain disorders. This review is focused on the new developments in oxidative stress-induced neurodegeneration. Further, based on our own investigations, new roles of quercetin, an antioxidant compound in hypoxia and ischemia induced neuroprotection in relation to suppression of oxidative stress, improvement in behavioral function, reduction in infarct volume, brain swelling, and cellular injury in both in vivo and in vitro models are discussed. Our new findings clearly suggest that antioxidant compounds have potential role in therapeutic strategies to treat neurodegenerative diseases in clinical settings.

  • 20. Ruozi, Barbara
    et al.
    Belletti, Daniela
    Forni, Flavio
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin
    Moessler, Herbert
    Vandelli, Maria A.
    Tosi, Giovanni
    Sharma, Hari S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Poly (D, L-Lactide-co-Glycolide) Nanoparticles Loaded with Cerebrolysin Display Neuroprotective Activity in a Rat Model of Concussive Head Injury2014In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 13, no 8, 1475-1482 p.Article in journal (Refereed)
    Abstract [en]

    Cerebrolysin (CBL) is a neuroprotective agent in central nervous system (CNS) injury and stimulates neurorepair processes. Several studies in our laboratory suggest that CBL administered through nanowired technology may have superior neuroprotective efficacy in CNS trauma. In this investigation, we compared the neuroprotective efficacy of poly-lactide-co-glycolide nanoparticles (NPs) loaded with CBL vs free CBL in a rat model of concussive head injury (CHI). Free CBL or CBL loaded NPs was administered 30 min to 1 h after CHI and animals were sacrificed 5 h later. Changes in blood-brain barrier and brain edema formation were measured as parameters of neuroprotection in CHI after giving CBL alone or as the nanodelivered compound. Our results clearly show that delivery of CBL by NPs has superior neuroprotective effects following CHI as compared to normal CBL. This suggests that CBL delivered by NPs could have robust neuroprotective action in CNS trauma. These findings have potential clinical relevance with regard to nanodelivery of CBL, a feature that requires further investigation.

  • 21.
    Ruozi, Barbara
    et al.
    Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
    Belletti, Daniela
    Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Univ Med & Pharm, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania..
    Moessler, Herbert
    Ever Neuro Pharma, Oberburgau, Austria..
    Forni, Flavio
    Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
    Vandelli, Maria Angela
    Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
    Tosi, Giovanni
    Univ Modena & Reggio Emilia, Dept Life Sci, Lab Pharmaceut Technol, I-41125 Modena, Italy..
    PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury2015In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 899-912 p.Article in journal (Refereed)
    Abstract [en]

    Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 +/- 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.

  • 22.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Menon, Preeti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Univ Med Pharm, Dept Clin Neurosci, Cluj Napoca, Romania.;RoNeuro Inst Neurol Res & Diagnost, 37 Mircea Eliade St, Cluj Napoca 400364, Romania..
    Ozkizilcik, Asya
    Univ Arkansas, Dept Biomed Engn, Fayetteville, AR 72701 USA..
    Tian, Z. Ryan
    Univ Arkansas, Chem & Biochem, Fayetteville, AR 72701 USA..
    Lafuente, Jose V.
    Univ Basque Country, UPV EHU, Dept Neurosci, Lab Clin & Expt Neurosci LaNCE, Leioa, Bizkaia, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
    Sharma, Hari S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair2016In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 15, no 9, 1092-1117 p.Article, review/survey (Refereed)
    Abstract [en]

    The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

  • 23.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Huang, H.
    Tian, Z. R.
    Moeessler, H.
    Sharma, H. S.
    Superior Neuroprotective Efficacy of Nanodrug Delivery of Cerebrolysin Compared to Other Neurotrophic Factors in Concussive Head Injury2014In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 23, no 6, 782-782 p.Article in journal (Other academic)
  • 24.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Lafuente, J. V.
    Sharma, Hari Shanker
    Engineered nanoparticles Ag, Cu and Al (50-60nm) induce oxidative stress, neuronal nitric oxide synthase upregulation and brain pathology. Neuroprotection by Insulin-like growth factor12012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, 441-441 p.Article in journal (Other academic)
  • 25.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Age- and size-dependent neurotoxicity of engineered nanoparticles from metals2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, 440-440 p.Article in journal (Other academic)
  • 26.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Blood-Brain Barrier Breakdown and Brain Dysfunction Following Sleep Deprivation Are Exacerbated by Size-Related Nanoparticles2013In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, no 5, 915-915 p.Article in journal (Other academic)
  • 27.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Univ Med & Pharm, Clin Neurosci.;RoNeuro Inst Neurol Res & Diagnost, Neurol..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Co-administration of nanowired mesenchymal stem cells and cerebrolysin potentiates neuroprotection in Parkinsons disease following mild traumatic brain injury2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, 19-19 p.Article in journal (Other academic)
  • 28.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D.
    Univ Med & Pharm, Clin Neurosci, Cluj Napoca, Romania..
    Lafuente, J.
    Univ Basque Country, Neurosci, Bilbao, Spain..
    Patnaik, R.
    Banaras Hindu Univ IIT, Biomed Engn, Varanasi, Uttar Pradesh, India..
    Moessler, H.
    Ever Neuro Pharma, Drug Dev & Discovery, Oberburgau, Austria..
    Tian, Z.
    Univ Arkansas Faytteville, Chem & Biochem, Faytteville, AK USA..
    Ozkizilcik, A.
    Univ Arkansas Faytteville, Chem & Biochem, Faytteville, AK USA..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Intoxication of engineered nanoparticles in cold environment exacerbates ischemia and brain pathology following trauma2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, 266-266 p., 400Article in journal (Other academic)
  • 29.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Univ Med & Pharm, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania..
    Lafuente, Jose V.
    Univ Basque Country, Dept Neurosci, Bilbao, Spain..
    Patnaik, Ranjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Banaras Hindu Univ, Indian Inst Technol, Dept Biomat, Sch Biomed Engn, Varanasi 221005, Uttar Pradesh, India..
    Tian, Z. Ryan
    Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA..
    Buzoianu, Anca D.
    Univ Med & Pharm, Fac Med, Dept Pharmacol, Cluj Napoca, Romania..
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron2015In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 867-881 p.Article in journal (Refereed)
    Abstract [en]

    Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB disruption and brain pathology, (ii) nanoparticles exacerbate SD-induced brain damage, and (iii) serotonin 5-HT3 receptor antagonist ondansetron is neuroprotective in SD that is further potentiated byTiO2-nanowired delivery, not reported earlier.

  • 30.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Patnaik, Ranjana
    Sharma, Hari S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Size- and Age-Dependent Neurotoxicity of Engineered Metal Nanoparticles in Rats2013In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 48, no 2, 386-396 p.Article in journal (Refereed)
    Abstract [en]

    Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50-60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood-brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier.

  • 31.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin Fior
    Moessler, Herbert
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Superior Neuroprotective Effects of Cerebrolysin in Nanoparticle-Induced Exacerbation of Hyperthermia-Induced Brain Pathology2012In: CNS & Neurological Disorders - Drug Targets, ISSN 1871-5273, Vol. 11, no 1, 7-25 p.Article, review/survey (Refereed)
    Abstract [en]

    In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed.

  • 32.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin Fior
    Patnaik, Ranjana
    Prasad, Vannemreaddy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Anaesthetics influence closed head injury induced blood-brain barrier disruption, cerebral blood flow, brain oedema and brain pathology2014In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 28, no 5-6, 522-523 p.Article in journal (Other academic)
  • 33.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin
    Univ Med & Pharm, Cluj Napoca, Romania..
    Lafuente, Jose V.
    Univ Basque Country, Bilbao, Spain..
    Patnaik, Ranjana
    BHU, Indian Inst Technol, Varanasi, Uttar Pradesh, India..
    Tian, Z. Ryan
    Univ Arkansas, Faytteville, AR USA..
    Moessler, Herbert
    Ever NeuroPharma, Oberburgau, Austria..
    Sharma, Hari S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Uppsala Hosp, Uppsala, Sweden..
    Cold environment exacerbates brain pathology and oxidative stress following traumatic brain injuries. Potential therapeutic effects of nanowired cerebrolysin2016In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 30, no 5-6, 506-506 p.Article in journal (Other academic)
  • 34.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin
    Moessler, Herbert
    Lafuente, Jose Vicente
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sleep Deprivation Exacerbates Pathophysiology of Concussive Head Injury: Neuroprotective Effects of a Multimodal Drug Cerebrolysin2015In: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 30, no 3, E80-E80 p.Article in journal (Other academic)
  • 35.
    Sharma, Aruna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Chapter 2: Monoclonal antibodies as novel neurotherapeutic agents in CNS injury and repair2012In: New Perspectives of Central Nervous System Injury and Neuroprotection / [ed] Sharma, HS, Elsevier, 2012, 23-45 p.Chapter in book (Refereed)
    Abstract [en]

    Central nervous system (CNS) injury is a complex in which numerous neurochemicals and other vasoactive agents actively contribute towards the development of posttraumatic brain pathology and/or repair mechanisms. A focal trauma to the brain or spinal cord releases several endogenous neurodestructive agents within the CNS, resulting in adverse cellular reactions. Our laboratory is engaged in identifying these endogenous neurodestructive signals in the CNS following injury caused by trauma or hyperthermia. Our observations show that serotonin (5-HT), dynorphin A (Dyn A 1-17), nitric oxide synthase (NOS), and tumor necrosis factor-α (TNF-α) could be potential neurodestructive signals in the CNS injury. Thus, neutralization of these agents using monoclonal antibodies directed against 5-HT, NOS, Dyn A (1-17), and TNF-α in vivo will result in marked neuroprotection and enhance neurorepair after trauma. In addition, a suitable combination of monoclonal antibodies, for example, NOS and TNF-α, when applied 60-90 min after trauma, is capable to enhance neuroprotective ability and thwart cell and tissue injury after spinal cord insult. Taken together, our novel observations suggest a potential use of monoclonal antibodies as suitable therapeutic agents in CNS injuries to achieve neuroprotection and/or neurorepair.

  • 36.
    Sharma, H.
    et al.
    Uppsala Univ Hsopital, Surg Sci Anesthesiol Intens Care Med, Uppsala, Sweden..
    Nozari, A.
    Massachusetts Gen Hosp, Anesthesiol & Intens Care Med, Boston, MA 02114 USA..
    Muresanu, D.
    Univ Med & Pharm, Clin Neurosci, Cluj Napoca, Romania..
    Moessler, H.
    Ever Neuro Pharma, Drug Dev & Discovery, Oberburgau, Austria..
    Lafuente, J.
    Univ Basque Country, Neurosci, Bilbao, Spain..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    NANOPARTICLES FROM METALS EXACERBATE CARDIAC ARREST INDUCED BRAIN PATHOLOGY. NEUROPROTECTIVE EFFECTS OF CEREBROLYSIN2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, 332-333 p., 476Article in journal (Other academic)
  • 37.
    Sharma, Hari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin
    Univ Med & Pharm, Cluj Napoca, Romania..
    Lafuente, Jose
    Univ Basque Country, Bilbao, Spain..
    Patnaik, Ranjana
    BHU, Indian Inst Technol, Varanasi, Uttar Pradesh, India..
    Moessler, Herbert
    Ever Neuropharma, Oberburgau, Austria..
    Tian, Z. Ryan
    Univ Arkansas, Fayetteville, AR 72701 USA..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanodrug delivery of a multimodal novel drug cerebrolysin reduces engineered nanoparticles induced aggravation of heat stroke induced ubiquitin expression and brain pathology2016In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 30, no 5-6, 505-506 p.Article in journal (Other academic)
  • 38.
    Sharma, Hari S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Patnaik, Ranjana
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Exacerbation of Brain Pathology After Partial Restraint in Hypertensive Rats Following SiO2 Nanoparticles Exposure at High Ambient Temperature2013In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 48, no 2, 368-379 p.Article, review/survey (Refereed)
    Abstract [en]

    This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 A degrees C) or at 33 A degrees C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine (([131]-)Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 A degrees C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.

  • 39.
    Sharma, Hari S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, Dafin F.
    Univ Med & Pharm, Dept Clin Neurosci, Cluj Napoca, Romania.;RoNeuro Inst Neurol Res & Diagnost, 37 Mircea Eliade St, Cluj Napoca 400364, Romania..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Alzheimer's disease: cerebrolysin and nanotechnology as a therapeutic strategy2016In: NEURODEGENERATIVE DISEASE MANAGEMENT, ISSN 1758-2024, Vol. 6, no 6, 453-456 p.Article in journal (Refereed)
  • 40.
    Sharma, Hari S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skaper, Stephen D.
    Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    8th Clinical Trials on Alzheimer Disease (CTAD), Barcelona, Spain November 5-7, 20152016In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 15, no 4, 375-377 p.Article in journal (Other academic)
  • 41.
    Sharma, Hari S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skaper, Stephen D.
    Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Novel Concepts on the Blood-Brain Barrier and Brain Pathology. New Therapeutic Approaches2016In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 15, no 9, 1014-1015 p.Article in journal (Other academic)
  • 42.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castellani, Rudy J
    Smith, Mark A
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The blood-brain barrier in Alzheimer's disease: novel therapeutic targets and nanodrug delivery2012In: New Perspectives of Central Nervous System Injury and Neuroprotection / [ed] Sharma, HS, Elsevier, 2012, 47-90 p.Chapter in book (Refereed)
    Abstract [en]

    Treatment strategies for Alzheimer's disease (AD) are still elusive. Thus, new strategies are needed to understand the pathogenesis of AD in order to provide suitable therapeutic measures. Available evidences suggest that in AD, passage across the blood-brain barrier (BBB) and transport exchanges for amyloid-β-peptide (ABP) between blood and the central nervous system (CNS) compartments play an important regulatory role for the deposition of brain ABP. New evidences suggest that BBB is altered in AD. Studies favoring transport theory clearly show that ABP putative receptors at the BBB control the level of soluble isoform of ABP in brain. This is achieved by regulating influx of circulating ABP into brain via specific receptor for advanced glycation end products (RAGE) and gp330/megalin-mediated transcytosis. On the other hand, the efflux of brain-derived ABP into the circulation across the vascular system via BBB is accomplished by low-density receptor-related protein-1 (LRP1). Furthermore, an increased BBB permeability in AD is also likely since structural damage of endothelial cells is quite frequent in AD brain. Thus, enhanced drug delivery in AD is needed to induce neuroprotection and therapeutic success. For this purpose, nanodrug delivery could be one of the available options that require active consideration for novel therapeutic strategies to treat AD cases. This review is focused on these aspects and provides new data showing that BBB plays an important role in AD-induced neurodegeneration and neurorepair.

  • 43.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Feng, Lianyuan
    Lafuente, Jose V.
    Muresanu, Dafin F.
    Tian, Zhenrong R.
    Patnaik, Ranjana
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes-Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches2015In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 14, no 3, 386-399 p.Article in journal (Refereed)
    Abstract [en]

    We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38 degrees C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x10(6)) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.

  • 44.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kiyatkin, Eugene A.
    NIDA, Vivo Electrophysiol Unit, Behav Neurosci Branch, IRP,NIH, Baltimore, MD USA..
    Patnaik, Ranjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lafuente, Jose Vicente
    Univ Basque Country, Dept Neurosci, Bilbao, Spain..
    Muresanu, Dafin F.
    Univ Med & Pharm, Univ Hosp, Dept Clin Neurosci, Cluj Napoca, Romania..
    Sjoquist, Per-Ove
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden..
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/512015In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 1023-1033 p.Article in journal (Refereed)
    Abstract [en]

    In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Molndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 A degrees C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 A degrees C, 120-180 % larger at 34 A degrees C, and almost absent at 4 A degrees C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 A degrees C, a four- to sixfold increase at 34 A degrees C, and three- to fourfold increase at 4 A degrees C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 A degrees C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.

  • 45.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Menon, Preeti K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lafuente, Jose Vicente
    Aguilar, Zoraida P.
    Wang, Y. Andrew
    Muresanu, Dafin Fior
    Moessler, Herbert
    Patnaik, Ranjana
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The Role of Functionalized Magnetic Iron Oxide Nanoparticles in the Central Nervous System Injury and Repair: New Potentials for Neuroprotection with Cerebrolysin Therapy2014In: Journal of Nanoscience and Nanotechnology, ISSN 1533-4880, E-ISSN 1533-4899, Vol. 14, no 1, 577-595 p.Article, review/survey (Refereed)
    Abstract [en]

    Functionalized Magnetic Iron Oxide Nanoparticles (FMIONPs) are being explored for the development of various biomedical applications, e.g., cancer chemotherapy and/or several other radiological or diagnostic purposes. However, the effects of these NPs per se on the central nervous system (CNS) injury or repair are not well known. This review deals with different aspects of FMIONPs in relation to brain function based on the current literature as well as our own investigation in animal models of CNS injuries. It appears that FMIONPs are innocuous when administered intravenously within the CNS under normal conditions. However, abnormal reactions to FMIONPs in the brain or spinal cord could be seen if they are combined with CNS injuries e.g., hyperthermia or traumatic insults to the brain or spinal cord. Thus, administration of FMIONPs in vivo following whole body hyperthermia (WBH) or a focal spinal cord injury (SCI) exacerbates cellular damage. Since FMIONPs could help in diagnostic purposes or enhance the biological effects of radiotherapy/chemotherapy it is likely that these NPs may have some adverse reaction as well under disease condition. Thus, under such situation, adjuvant therapy e.g., Cerebrolysin (Ever NeuroPharma, Austria), a suitable combination of several neurotrophic factors and active peptide fragments are the need of the hour to contain such cellular damages caused by the FMIONPs in vivo. Our observations show that co-administration of Cerebrolysin prevents the FMIONPs induced pathologies associated with CNS injuries. These observations support the idea that FMIONPs are safe for the CNS in disease conditions when co-administered with cerebrolysin. This indicates that cerebrolysin could be used as an adjunct therapy to prevent cellular damages in disease conditions where the use of FMIONPs is required for better efficacy e.g., cancer treatment.

  • 46.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Menon, Preeti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lafuente, Jose Vicente
    Muresanu, Dafin F.
    Tian, Z. Ryan
    Patnaik, Ranjana
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Development of in vivo drug-induced neurotoxicity models2014In: Expert Opinion on Drug Metabolism & Toxicology, ISSN 1742-5255, E-ISSN 1744-7607, Vol. 10, no 12, 1637-1661 p.Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Neurotoxicity caused by diverse psychostimulant drugs, for example, methamphetamine, 3,4-methylenedioxy-methamphetamine, cocaine or morphine is a cause of concern to human populations especially the young generation across the world. These recreational drugs affect brain function severely leading to addiction and brain pathology. Use of psychostimulants may induce breakdown of the blood-brain barrier to serum proteins resulting in adverse brain microenvironment, edema cell injury or eventually neuronal death. Thus, there is an urgent need to find out detailed mechanisms of psychostimulants-induced neurotoxicity in vivo models for suitable therapeutic strategies to induce neuroprotection and also to help de-addiction in clinical situations. Areas covered: In this review, psychostimulants drugs-induced neurotoxicity is discussed in view of recent literature and the financial burden it may pose on our society due to rehabilitation and de-addiction. Furthermore, experimental evidences of drug-induced neuroprotection are also discussed. Expert opinion: Use of in vivo models of neurotoxicity caused by psychostimulants is discussed based on author's own research and to find suitable drugs that could induce neuroprotection including nanodelivery. Furthermore, novel therapeutic agents for de-addiction and reducing neurotoxicity following psychostimulants administration are presented.

  • 47.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Exacerbation of Stress Symptoms, Sensory Motor Dysfunction, and Brain Pathology After Partial Restraint in Hypertensive Rats Following Silica Dust (SiO2 Nanoparticles) Exposure at High Ambient Temperature2012In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 21, no 4, 790-790 p.Article in journal (Other academic)
  • 48.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Patnaik, R.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanoparticles Exacerbate Brain Pathology and Sensory Motor Disturbances Following Concussive Brain Injury2013In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 22, no 5, 915-916 p.Article in journal (Other academic)
  • 49.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D. F.
    Smith, M. A.
    Smith, G. Casadesus
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Astrocytes are sensitive indicators of hyperthermia-induced brain oedema in normal and in Cu nanoparticles treated rats2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, 420-420 p.Article in journal (Other academic)
  • 50.
    Sharma, Hari Shanker
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Muresanu, D.
    Nozari, A.
    Patnaik, R.
    Moessler, H.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nanoparticles Aggravate Cardiac Arrest-Induced Blood-Brain Barrier Breakdown, Edema Formation, and Neuronal Injuries: Neuroprotective Effects of a Multimodal Drug Cerebrolysin2014In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 23, no 6, 782-783 p.Article in journal (Other academic)
12 1 - 50 of 85
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