PHARMACOLOGICAL BRAIN PROTECTION - SPECIF IC AGENTS

Dysfunctional sodium influx is the first step in the ischaemic cascade . It has been recently demonstrated that reducing ionic flux through v oltage-gated Na channels shortens the NMDA receptor activity of cultur ed hippocampal slices in which oxidative phosphorylation and glycolysi s 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 event s. It also seems intuitively reasonable to suppose that truncating ini tial steps of the ischaemic cascade, as distinct from blocking glutama te receptors and scavening free radicals, will reduce the probability of interferring with endogenous mechanisms of repair. Clinically usefu l, substantive, prophylactic, pharmacological cerebral protection will come from drugs that work upstream. And for pharmacological protectio n that can only be initiated subsequent to an ischaemic event, the mor e we learn about endogenous repair, or genetic pharmacology, the close r we will come to maximizing the benefits and minimizing the costs of downstream intervention.