Contribution of purinergic receptors to spinal cord injury repair: stem cell- based neuroregeneration

Afterwards, a cascade of secondary pathophysiological mechanisms is induced, including ischemia, apoptosis, fluid and electrolyte disturbances, excitotoxicity, lipid peroxidation, production of free radicals, and an inflammatory response, resulting in further damage due to swelling and blood flow reduction (Tator et al., 2012). Neurospheres derived from the adult mouse SVZ express P2X4 and P2X7 mRNA, and have functional P2Y 1 and P2Y 2 receptors, whose activation increases cell proliferation in the presence of growth factors and stimulates the migration of neural progenitors isolated in vitro and expanded as neurospheres, which may be of relevance for the local movement of cells in the neurogenic niches. [...]P2Y 1 receptor antagonists reduce neurosphere size and neurosphere-forming frequency of primary neurospheres derived from adult mouse SVZ, allowing the possibility that a proportion of the neural progenitor cell population differentiates into neurons and glia. A comparative genetic profile analysis reveals the upregulation of proinflamatory signalling cascades, including vascular endothelial growth factor (VEGF)/mitogen-activated protein kinases (MAPK) and Jak/Stat pathways, in epSPCis compared to epSPCs derived from healthy donors (Moreno-Manzano et al., 2009). [...]a comparative study between epSPCs versus epSPCis reveals that a downregulation of P2Y 1 receptor together with an upregulation of P2Y 4 receptor occur in epSPCis (Gomez-Villafuertes et al., 2015). P2Y 1 receptor downregulation could be facilitating the differentiation of epSPCis into neuronal/glial cells that participate in the improvement of functional locomotor recovery observed after epSPCi transplantation, while an increment in P2Y 4 receptor expression in epSPCis could increase the expansion and mitotic index of neural progenitor cells within those neurospheres.