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Induction of Acute Ischemic Stroke in Mice Using the Distal Middle Artery Occlusion Technique
Published on: December 15, 2023
Sonic hedgehog signaling pathway mediates cerebrolysin-improved neurological function after stroke
Li Zhang1, Michael Chopp, Dieter H Meier
1Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
Stroke
|May 23, 2013
Summary
Cerebrolysin enhances neurogenesis and recovery after stroke by activating the Sonic hedgehog (Shh) pathway. Blocking this pathway with cyclopamine reverses these beneficial effects in rats.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pharmacology
Background:
- Cerebrolysin, a neurotrophic peptide mixture, shows promise in treating neurodegenerative diseases and stroke.
- The Sonic hedgehog (Shh) signaling pathway is known to promote neurogenesis post-stroke.
Purpose of the Study:
- To investigate if the Shh pathway mediates the neurogenic and neurorestorative effects of Cerebrolysin after stroke.
- To determine the role of Shh signaling in Cerebrolysin-induced neurogenesis and functional recovery.
Main Methods:
- Adult rats with embolic stroke were treated with Cerebrolysin, with or without the Shh pathway inhibitor cyclopamine.
- Neural progenitor cell proliferation and differentiation were assessed in vitro and in vivo.
- Neurological function was evaluated in treated and control rats.
Main Results:
- Cerebrolysin increased neural progenitor cell proliferation and differentiation into neurons and oligodendrocytes in vitro, associated with Shh pathway activation.
- In ischemic rats, Cerebrolysin promoted neurogenesis, oligodendrogenesis, and axonal remodeling, leading to significant functional recovery.
- Inhibition of the Shh pathway with cyclopamine abolished Cerebrolysin's positive effects on neurorestoration and functional recovery.
Conclusions:
- The Shh signaling pathway is essential for Cerebrolysin's ability to enhance neurogenesis and white matter remodeling.
- Cerebrolysin-induced functional recovery after stroke is mediated through the Shh pathway.
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