Regional Recovery from Global Cerebral Ischemia

抄録

To understand the molecular mechanisms of ischemic injury, it is important to determine regional metabolic alterations during and after cerebral ischemia. Mild, incomplete ischemia causes metabolic change first in cerebral white matter, and the subsequent alterations in gray matter exhibit marked microheterogeneity. By contrast, recovery from transient global ischemia is characterized by macroscopic focal energy failure. The regions with impaired energy metabolism exhibit decreased rather than increased NADH fluorescence and suffer a decrease in the total pool of NADH+NAD⁺. These changes suggest a defect in the generation of NADH that could impair postischemic recovery of energy metabolism. Since NADH is unstable in acid, the glucose-induced enhancement of lactic acidosis may be responsible forpremature diminution of the NAD pool and subsequent energy failure. However, this hypothesis is not supported experimentally since ischemic insults that generate high concentrations of lactic acid do not produce a greater decrease in the NAD pool. During postischemic reperf usion in the gerbil, pyruvate dehydrogenase (PDH ) is markedly inhibited. Administration of dichloroacetate (DCA), an activator of PDH, has no effect of PDH activity or recovery of metabolites early during reperf usion. However, at 4 hr reperf usion, DCA activates PDH and prevents secondary energy failure in the caudate nucleus. Thus, postischemic inhibition of PDH may limit recovery of energy metabolism following cerebral ischemia.