POTENTIAL THERAPEUTIC INTERVENTION FOLLOWING HYPOXIC-ISCHEMIC INSULT

Cell caused by hypoxia-ischemia appears to be due to multiple mechanis ms causing lysis of cells, both by osmotic rupture and by calcium-depe ndent activation of degradative processes, as well as apoptosis. In th e case of osmotic and calcium-dependent lysis, the triggering stimulus seems to be abnormal accumulation of glutamate in the extracellular s pace. In the case of apoptotic death, the triggering stimulus is uncle ar, Because activation of one or more death programs does not necessar ily commit a cell to die, a therapeutic window exists in which it shou ld be possible to intervene to prevent progression to cell death in ma ny cells that are affected by an hypoxic-ischemic episode. Several the rapeutic approaches have emerged targeting various steps in the proces s set in motion by abnormal glutamate accumulation. In addition, other approaches need to be developed to block apoptotic cell death. The mo st efficacious forms of therapy will probably be those that are effect ive against all types of cell death triggered by hypoxia-ischemia. Thi s may be accomplished either by the use of multiple agents or by inter vention targeting processes or intermediates shared by multiple mechan isms of cell death. (C) 1997 Wiley-Liss, Inc.