[Cerebral protection]

Sodium influx is the first step in the ischemic cascade. Vornov et al. recently demonstrated that reducing ionic flux through voltage-gated Na channels shortens the NMDA receptor activity of cultured hippocampal slices in which oxidative phosphorylation and glycolysis have been blocked. The implication of this finding is that blocking initial events in the ischemic cascade, events which do not directly cause neuronal damage, will reduce the damage done by downstream events. It also seems intuitively reasonable to suppose that truncating initial steps of the ischemic cascade, as distinct from blocking glutamate receptors and scavenging free radicals, will reduce the probability of interfering with endogenous mechanisms of repair. My guess is that clinically useful, substantive, prophylactic, pharmacological cerebral protection will come from drugs that work upstream in the ischemic cascade. For pharmacological protection that can only be initiated subsequent to an ischemic event, free radical scavengers probably hold the most promise for clinical efficacy.