Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury

Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation cell proliferation through modulation the sonic hedgehog pathway, key NSC regulatory could lead functional improvement. assessed (Shh) protein levels in cerebrospinal fluid (CSF) patients with TBI. Using cortical contusion (CCI) model rodents, we used pharmacological modulators Shh signaling assess within injured cortex using marker 5-Ethynyl-2’-deoxyuridine (EdU); 50mg/mL. The phenotype proliferating was determined quantified. Motor function rotarod test. In TBI there reduction CSF compared control patients. following severe CCI, quiescent become activated. Pharmacologically modulating pathway leads changes number newly injury-induced cells. Upregulation Smoothened agonist (SAG) results an increase expressing glial fibrillary acidic (GFAP), whereas inhibitor cyclopamine reduction. Some expressed doublecortin (DCX) but did not mature into neurons. SAG-induced associated improved recovery motor function. Localized restoration rodent brain, via increased signaling, potential sustain mitigation TBI-induced deficits albeit without neuronal differentiation.