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Nanowired Delivery of Cerebrolysin and Mesenchymal Stem Cells Potentiate Neuroprotection Following Concussive Head Injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Univ Med & Pharm, Cluj-Napoca, Romania.
Univ Basque Country, Bilbao, Spain.
Banaras Hindu Univ, Varanasi, Uttar Pradesh, India.
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2017 (English)In: The journal of head trauma rehabilitation, ISSN 0885-9701, E-ISSN 1550-509X, Vol. 32, no 6, p. E67-E68Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction/Rational: Military personnel are highly vulnerable to concussive head injury (CHI) during combat operations resulting in long-term disability. Since no suitable treatments are available novel therapeutic strategies using combination therapy is needed. Since, stem cells and/or neurotrophic factors are shown to induce neuroprotection in central nervous system (CSN) injuries and nanodelivery of therapeutic agents have superior effects on neuroprotection in brain injury, in this investigation we used nanowired delivery of mesenchymal stem cells (MSCs) together with a multimodal drug cerebrolysin- a powerful combination of various neurotrophic factors and active peptide fragments in CHI to induce neuroprotection in CHI.

Method/Approach: CHI was inflicted in rats using a weight drop of 114.6 g on the right parietal skull under Equithesin anesthesia from a 20 cm height causing an impact of 0.224 N and mimic the “counter-coup” phenomenon as seen 48 h after the primary insult. In separate groups, commercially available MSCs (1 million cells) in combination with Cerebrolsyin (2.5 ml/kg; Ever NeuroPharma, Austria) either as such or with TiO2 nanowired formulations were delivered intravenously 4 and 8 after CHI. After 48 h CHI blood-brain barrier (BBB) to Evans blue and radioiodine, brain edema and neuronal injuries were examined.

Results/Effects: A focal CHI induced massive breakdown of the BBB to Evans blue albumin and [131]-Iodine and volume swelling at 48 h that was significantly higher in the left hemisphere as compared to the right side. Neuronal damages using Nissl staining was also prominent in the cortex, hippocampus, thalamus and hypothalamus in the left side. Treatment with TiO2 nanowired MSCs and cerebrolysin resulted in significant reduction in brain pathology that was seen in both the right and left hemispheres. Whereas, normal MSCs and cerebrolysin were able to reduce brain pathology largely in the right side only.

Conclusions/Limitations: These observations are the first to demonstrate that a combination of nanowired Cerebrolsyin and MSCs synergistically induced efficient neuroprotection in CHI, not reported earlier. It would be interesting to see whether this combination when administered 8 or 12 h after CHI whether neuroprotective effects are still visible at 48 h, a feature currently being investigated in our laboratory.

Place, publisher, year, edition, pages
2017. Vol. 32, no 6, p. E67-E68
National Category
Neurosciences Neurology
Identifiers
URN: urn:nbn:se:uu:diva-347728DOI: 10.1097/HTR.0000000000000241ISI: 000418588100015OAI: oai:DiVA.org:uu-347728DiVA, id: diva2:1197024
Conference
North American Brain Injury Society's 13th Annual Conference on Brain Injury, April 6-9, 2016, Tampa, Florida, USA.
Note

Meeting Abstract: 0008

Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved

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Sharma, Hari ShankerSharma, Aruna

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