GR.6 Harnessing the endogenous regenerative potential of the injured spinal cord

Background: The adult spinal cord contains a population of ependymal-derived neural stem/progenitor cells (epNSPCs) with the potential to enhance endogenous regeneration. However, little is known about mechanisms that regulate activation these after injury. Recently, we discovered glutamate excitotoxicity, hallmark in pathophysiology acute SCI, promotes epNSPC proliferation/survival. Here, characterize downstream signaling pathways involved this response and target mechanism vivo regenerative capacity cells. Methods: epNSPCs were isolated from central canal region cord. In vitro pathway analysis was conducted using immunohistochemistry, RNAseq Western Blot. , rats underwent SCI at 1-week post-injury randomized receive CX546 (positive AMPAR modulator), or vehicle-control. Animals behavioural testing cords extracted for analysis. Results: Glutamate excitotoxicity leads calcium influx via AMPARs together Notch drives proliferation astrocytic differentiation. Positive modulation subacutely enhances proliferation, astrogliogenesis, neurotrophin production, neuronal survival functional recovery. Conclusions: We uncover an important by which growth/phenotype can be targeted therapeutically harness injured