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Timed Release of Cerebrolysin Using Drug-Loaded Titanate Nanospheres Reduces Brain Pathology and Improves Behavioral Functions in Parkinson's Disease
Univ Arkansas, Dept Biomed Engn, Fayetteville, AR 72701 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, Univ Hosp, Int Expt CNS Injury & Repair IECNSIR, Frodingsgatan 12,Bldg 28, SE-75421 Uppsala, Sweden..
Univ Med & Pharm, Dept Clin Neurosci, Cluj Napoca, Romania.;RoNeuro Inst Neurol Res & Diagnost, 37 Mircea Eliade St, Cluj Napoca 400364, Romania..
Univ Basque Country UPV EHU, Dept Neurosci, LaNCE, Leioa, Biscay, Spain.;BioCruces Hlth Res Inst, Nanoneurosurg Grp, Baracaldo 48903, Biscay, Spain.;Univ Autonoma Chile, Fac Hlth Sci, Santiago, Chile..
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 359-369Article in journal (Refereed) Published
Abstract [en]

Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD. Since cerebrolysin (CBL) is a well-balanced composition of several neurotrophic factors and active peptide fragments, in the present investigation we examined the timed release of CBL using titanate nanospheres (TiNS) in treating PD in our mouse model. Our observations show that TiNS-CBL (in a dose of 3 ml/kg, i.v.) given after 2 days of MPTP administration for 5 days resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also, TiNS-CBL resulted in significantly higher levels of DA, DOPAC, and HVA in SNpc and STr on the 8th day as compared to normal CBL therapy. TiNS-CBL also thwarted increased alpha-synuclein levels in the brain and in the cerebrospinal fluid (CSF) as well as neuronal nitric oxide synthase (nNOS) in the in PD brain as compared to untreated group. Behavioral function was also significantly improved in MPTP-treated animals that received TiNS-CBL. These observations are the first to demonstrate that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL.

Place, publisher, year, edition, pages
HUMANA PRESS INC , 2018. Vol. 55, no 1, p. 359-369
Keywords [en]
1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridin (MPTP), Parkinson's disease (PD), Titanate nanospheres (TiNS), Cerebrolysin, Neuroprotection, Alpha-synuclein, Neuronal nitoic oxide synthase (nNOS), Cerebrospinal fluid (CSF)
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-347258DOI: 10.1007/s12035-017-0747-4ISI: 000424702600035PubMedID: 28875428OAI: oai:DiVA.org:uu-347258DiVA, id: diva2:1194455
Funder
Swedish Research Council, 2710-HSSGöran Gustafsson Foundation for Research in Natural Sciences and MedicineAstraZenecaAvailable from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved

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Sharma, ArunaSharma, Hari Shanker

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