Neuroprotective and Proneurogenic Effects of Glucosamine in an Internal Carotid Artery Occlusion Model of Ischemia

Neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine, a naturally occurring amino sugar, have been reported in various animal models of brain injury including cerebral ischemia and hypoxic brain damage. Given that clinical translation of therapeutic candidates identified in animal models of ischemic stroke has remained unsatisfactory in general, possibly due to inadequacy of existing models, we sought to study the effects of glucosamine in a recently developed, clinical condition mimicking mouse model of internal cerebral artery occlusion. In this model of mild to moderate striatal damage, glucosamine ameliorated behavioral dysfunction, rescued ischemia-induced striatal damage, and suppressed ischemia-induced upregulation of proinflammatory genes in striatal tissue. Further, in ex vivo neurosphere assay involving neural stem cells/neural progenitor cells from subventricular zone, glucosamine increased the number of large neurospheres, along with enhancing mRNA levels of the proliferation markers Nestin, NeuroD1, and Sox2. Lastly, coronal brain sections containing the striatal region with subventricular zone showed increased number of BrdU positive cells and DCX positive cells, a marker for newly differentiating and immature neurons, in glucosamine-treated ischemic mice. Cumulatively, the results confirming neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine enhance drug repurposing potential of glucosamine in cerebral ischemia.