Membrane repair of damaged neurons by surfactant poloxamers has been noted in experimental spinal cord injury and in vitro excitotoxicity. We examined poloxamer-188 (P-188)-mediated neuroprotection in a rat model of glutamate toxicity. Quinolinate was infused into the striatum followed 10 min and 4 h later by P-188 administered either i.v. or intracisternally (i.c.), or by vehicle. Mean neuronal loss examined volumetrically 7 days later in control animals was 50% greater (P < 0.01) than after i.c. P-188 treatment; control lesion volumes were 38% greater than lesion volumes after i.v. P-188 treatment; however, that comparison did not reach significance. This robust protection against glutamate toxicity may predict P-188-mediated neuroprotection against a broad range of clinically relevant neural insults.