Autoprotective mechanisms in the CNS: some new lessons from white matter

Anoxia/ischemia in the CNS is a common and devastating phenomenon. It is possible that the best hopes for protection against anoxic/ischemic injury may involve recruiting and/or augmenting any autoprotective systems that evolution has provided for the CNS. We describe here the existence of such an autoprotective system present in CNS white matter. White matter is both well suited to studying extrasynaptic systems, such as the system we describe here, and is a highly appropriate target for research into anoxic-ischemic injury in its own right. We show that white matter contains functional GABAB and adenosine receptors that respond to an anoxic efflux of GABA and adenosine by recruiting a convergent intracellular mechanism involving protein kinase C (PKC). The net result of this receptor-mediated cascade is an increase in resistance to anoxia, which presumably allows CNS white matter to tolerate better a common class of ischemic events that are located solely in white matter and that comprises approximately 25% of all strokes seen clinically.