P.089 AMPA receptor modulation as a therapeutic strategy to enhance survival of spinal cord neural stem cells

Background: Transplantation of neural stem/progenitor cells (NSPCs) following spinal cord injury (SCI) is a promising strategy to enhance regeneration but is limited by poor survival of grafted cells. Recently, we demonstrated for the first time that the excitatory neurotransmitter glutamate, which is released after SCI, promotes survival/proliferation of spinal cord NSPCs via the AMPA subtype of glutamate receptors. Here, we examine the therapeutic potential of selective AMPA receptor modulation on NSPC survival using allosteric AMPA receptor modulators known as ampakines. Methods: NSPCs from the periventricular region of the adult rat spinal cord were treated with ampakines CX614 and CX546 for 72h either alone or in the presence of low-dose glutamate (50uM). Results: Treatment with CX-546 or CX-614 in the presence of glutamate led to a significant increase in live cell numbers. This was due to both a reduction in cell death and increase in cellular proliferation. Ampakine/glutamate treatment led to a significant increase in cell survival compared to controls in the setting of oxidative stress. Conclusions: We present the first examination of the effect of allosteric AMPA receptor modulators on adult spinal cord--derived NSPCs. Positive modulation of AMPA receptors may be a promising therapeutic strategy in the subacute/chronic phases after SCI to increase survival of endogenous or transplanted NSPCs.