HYPOXIC-ISCHEMIC BRAIN INJURY IN THE NEWBORN - CELLULAR MECHANISMS AND POTENTIAL STRATEGIES FOR NEUROPROTECTION

Recent advances have delineated many of the complex cellular mechanism s of cerebral hypoxic-ischemic injury. These developments have created opportunities for the design of rational '' mechanism-based '' strate gies that target specific injurious processes. A number of neuroprotec tive agents have entered adult clinical trial and practice. For the ne wborn infant, progress in this areas has been judiciously delayed by t oxicity concerns. Central to those safety concerns is the close relati onship between mechanisms of hypoxic-ischemic cellular injury and norm al developmental processes. These cellular mechanisms and the dilemmas facing the advance of this field are discussed. The likelihood of an effective single '' magic bullet '' neuroprotective strategy emerging in the near future appears remote. Rather more likely is the developme nt of '' cocktail '' therapies that seek to exploit synergistic antago nism at multiple levels in the complex concentration of cellular event s mediating hypoxic-ischemic cellular injury. However, such combinatio n therapies will require elucidation of the complex inter-relationship s between mechanisms of cellular injury, brain development, and the co mbination of therapies envisioned.