WHITE-MATTER STROKE - AUTO PROTECTIVE MECHANISMS WITH THERAPEUTIC IMPLICATIONS

The incidence of stroke involving CNS white matter is relatively high, yet there are currently no protective treatments that limit irreversi ble dysfunction in white matter stroke. The events that lead from the loss of oxygenation to irreversible injury in white matter are now wel l characterized. Anoxic injury in white matter follows the accumulatio n of toxic levels of Ca2+ within intracellular compartments. This Ca2 influx is triggered by depolarization, influx of Na+ and subsequent b ackward operation of a membrane protein, the Na+/Ca2+ exchanger, which normally moves Ca2+ out of cells. Anoxic injury in white matter is pa rtly under the control of autoprotective substances released by white matter. In particular, GABA and adenosine are released from endogenous stores as a result of anoxia and recruit a cascade of intracellular e vents which act to increase resistance to anoxic injury. Recovery of f unction in white matter following anoxic insults can be improved by ap plication of exogenous GABA or adenosine, and by exposure to drugs whi ch inhibit reuptake to increase the levels of GABA and adenosine in th e extracellular space. This autoprotective system is thus open to mani pulation via pharmacological strategies that may prove to be clinicall y useful.