Document Detail


Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.
MedLine Citation:
PMID:  20857512     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine-positive (BrdU(+)) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24 hr after stroke. The treatment also reduced TUNEL(+) cells by ∼50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48 hr did not significantly reduce infarct volume but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU(+) cells and increased the number of Tuj1(+) cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU(+) cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48 hr after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation.
Authors:
Chunling Zhang; Michael Chopp; Yisheng Cui; Lei Wang; Ruilan Zhang; Li Zhang; Mei Lu; Alexandra Szalad; Edith Doppler; Monika Hitzl; Zheng Gang Zhang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-12     Completed Date:  2011-01-25     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3275-81     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / pharmacology*
Animals
Blotting, Western
Brain Ischemia / drug therapy*,  pathology
Cell Differentiation / drug effects
Immunohistochemistry
Male
Neurogenesis / drug effects*,  physiology
Neurons / cytology,  drug effects,  metabolism
Neuroprotective Agents / pharmacology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Wistar
Recovery of Function / drug effects*
Signal Transduction / drug effects
Stem Cells / cytology,  drug effects,  metabolism
Stroke / drug therapy*,  pathology
Grant Support
ID/Acronym/Agency:
P01 NS023393/NS/NINDS NIH HHS; P01 NS023393-23/NS/NINDS NIH HHS; P01 NS23393/NS/NINDS NIH HHS; R01 HL064766/HL/NHLBI NIH HHS; R01 HL064766-08/HL/NHLBI NIH HHS; R01 HL64766/HL/NHLBI NIH HHS; R01 NS062832/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Neuroprotective Agents; 12656-61-0/cerebrolysin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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