Positive Modulation of AMPA Receptors Promotes Survival and Proliferation of Neural Stem/Progenitor Cells from the Adult Rat Spinal Cord.

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. Determining methods to enhance survival of NSPCs is therefore essential. Positive modulation of AMPA receptors has been shown to enhance neurogenesis in various models of brain injury. Here we examined the effect of selective AMPA receptor modulation in adult rat spinal cord-derived NSPCs using a class of allosteric AMPA receptor modulators known as ampakines. NSPCs from the periventricular region of the adult rat spinal cord were treated with ampakines CX614 and CX546 for 72 h either alone or in the presence of low-dose glutamate (50 μM). Treatment with either agent in the presence of glutamate significantly increased cell survival and proliferation and reduced cell death. Moreover, ampakine/glutamate treatment reduced cell death in the setting of oxidative stress. Treatment with ampakines did not significantly alter cell phenotype. These findings offer important insight into a potential therapeutic strategy to positively regulate transplanted and endogenous adult spinal cord-derived NSPCs after SCI.