[Pharmacologic brain protection: specific agents].

Abstract

Dysfunctional sodium influx is the first step in the ischaemic cascade. It has been recently demonstrated that reducing ionic flux through voltagegated 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 ischaemic 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 ischaemic cascade, as distinct from blocking glutamate receptors and scavening free radicals, will reduce the probability of interfering with endogenous mechanisms of repair. Clinically useful, substantive, prophylactic, pharmacological cerebral protection will come from drugs that work upstream. And for pharmacological protection that can only be initiated subsequent to an ischaemic event, the more we learn about endogenous repair, or genetic pharmacology, the closer we will come to maximizing the benefits and minimizing the costs of downstream intervention.