The Shh Signaling Pathway Is Upregulated in Multiple Cell Types in Cortical Ischemia and Influences the Outcome of Stroke in an Animal Model
Autor: | Nicholas C. Bambakidis, Austin Barnett, Yongmin Jin, Nataly Raviv, Emily Filichia, Yu Luo |
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Rok vydání: | 2015 |
Předmět: |
Male
Pathology medicine.medical_specialty Cell type animal structures lcsh:Medicine Subventricular zone Thiophenes Brain Ischemia Brain ischemia Mice medicine Animals Hedgehog Proteins Sonic hedgehog lcsh:Science Cerebral Cortex Cyclohexylamines Multidisciplinary Behavior Animal biology lcsh:R Nestin medicine.disease Neural stem cell Stroke Tamoxifen medicine.anatomical_structure nervous system Cerebral cortex embryonic structures biology.protein lcsh:Q Signal transduction Neuroscience Research Article Signal Transduction |
Zdroj: | PLoS ONE, Vol 10, Iss 4, p e0124657 (2015) PLoS ONE |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0124657 |
Popis: | Recently the sonic hedgehog (shh) signaling pathway has been shown to play an important role in regulating repair and regenerative responses after brain injury, including ischemia. However, the precise cellular components that express and upregulate the shh gene and the cellular components that respond to shh signaling remain to be identified. In this study, using a distal MCA occlusion model, our data show that the shh signal is upregulated both at the cortical area near the injury site and in the adjacent striatum. Multiple cell types upregulate shh signaling in ischemic brain, including neurons, reactive astrocytes and nestin-expressing cells. The shh signaling pathway genes are also expressed in the neural stem cells (NSCs) niche in the subventricular zone (SVZ). Conditional deletion of the shh gene in nestin-expressing cells both at the SVZ niche and at the ischemic site lead to significantly more severe behavioral deficits in these shh iKO mice after cortical stroke, measured using an automated open field locomotion apparatus (Student’s t-test, p0.05). In summary, our data demonstrate that shh signaling plays critical and ongoing roles in response to ischemic injury and modulation of shh signaling in vivo alters the functional outcome after cortical ischemic injury. |
Databáze: | OpenAIRE |
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