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Sonic hedgehog signaling pathway mediates cerebrolysin-improved neurological function after stroke.

Authors: Zhang, Li  Chopp, Michael  Meier, Dieter H  Winter, Stefan  Wang, Lei  Szalad, Alexandra  Lu, Mei  Wei, Min  Cui, Yisheng  Zhang, Zheng Gang 
Citation: Zhang L, etal., Stroke. 2013 Jul;44(7):1965-72. doi: 10.1161/STROKEAHA.111.000831. Epub 2013 May 21.
Pubmed: (View Article at PubMed) PMID:23696546
DOI: Full-text: DOI:10.1161/STROKEAHA.111.000831


BACKGROUND AND PURPOSE: Cerebrolysin, a mixture of neurotrophic peptides, enhances neurogenesis and improves neurological outcome in experimental neurodegenerative diseases and stroke. The Sonic hedgehog (Shh) signaling pathway stimulates neurogenesis after stroke. The present study tests whether the Shh pathway mediates cerebrolysin-induced neurogenesis and improves neurological outcome after stroke.
METHODS: Rats subjected to embolic stroke were treated with cerebrolysin with or without cyclopamine.
RESULTS: Using neural progenitor cells derived from the subventricular zone of the lateral ventricle of adult rats, we found that cerebrolysin significantly increased neural progenitor cells proliferation and their differentiation into neurons and myelinating oligodendrocytes, which were associated with upregulation of Shh and its receptors patched and smoothened. Blockage of the Shh signaling pathway with a pharmacological smoothened inhibitor, cyclopamine, abolished cerebrolysin-induced in vitro neurogenesis and oligodendrogenesis. In the ischemic rats, treatment with cerebrolysin starting 24 hours after stroke significantly increased neural progenitor cell proliferation in the subventricular zone and enhanced neurogenesis, oligodendrogenesis, and axonal remodeling in the peri-infarct area. Moreover, profound neurological function improvements were observed in rats treated with cerebrolysin from week 3 to week 5 after stroke onset compared with vehicle-treated rats. However, in vivo inhibition of the Shh pathway with cyclopamine completely reversed the effects of cerebrolysin on neurorestoration and functional recovery.
CONCLUSIONS: These results demonstrate that the Shh pathway mediates cerebrolysin-enhanced neurogenesis and white matter remodeling and improves functional recovery in rats after stroke.

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RGD Object Information
RGD ID: 12832759
Created: 2017-04-10
Species: All species
Last Modified: 2017-04-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.