Cortical death caused by striatal administration of AMPA and interleukin-1 is mediated by activation of cortical NMDA receptors

Striatal coadministration of interleukin-1 beta (IL-1 beta) with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA) in rats results in widespread cortical cell death not caused by either treatment alone. This cortical damage was unaffected by cortical infusion of the AMPA-receptor antagonist NBQX. Cortical infusion of an NMDA-receptor antagonist D-APS significantly inhibited (57%; P < 0.05) cortical death, but had no effect on the local striatal death. Thus, cortical neuronal death induced by striatal S-AMPA and human recombinant interleukin-1 beta (hrIL-1 beta) is mediated by activation of NMDA receptors in the cortex. The authors propose that IL-1 beta actions on AMPA-receptor mediated cell death may involve the activation of polysynaptic pathways from the striatum to the cortex.