SECONDARY MITOCHONDRIAL DAMAGE AND DELAYED NEURONAL DEATH IN HYPERGLYCEMIC RATS

The objective of the study was to explore if pre-ischemic hyperglycemi a exaggerates or accelerates neuronal damage in the hippocampus of rat s by inducing delayed mitochondrial dysfunction, and if signs of such dysfunction precede the development of morphologically detectable neur onal necrosis. Mitochondrial function in homogenates from dorsal CAI a nd CA3 and from ventral parts of hippocampus was examined in normo- (s imilar to 5 mM) and hyperglycemic (similar to 20 mM) rats subjected to 10 min of forebrain ischemia followed by 0, 6 and 16-18 h of reperfus ion. Histopathological changes were evaluated after 6 and 16-18 h of r ecovery by light microscopy. Since animals recirculated for 16-18 h ar e normoglycemic, respiratory variables in recirculated animals were co mpared to normoglycemic controls. The analyses failed to show dysfunct ion of mitochondria. Delayed neuronal damage in the CA1 sector of hipp ocampus was observed in 5/8 hyperglycemic rats after 16-18 h of recirc ulation, whereas no detectable morphological alterations were observed in hippocampus in normoglycemic rats. Since brain mitochondrial funct ion was normal when neuronal damage appeared, unaltered mitochondrial injury cannot be made responsible for delayed neuronal death. However, it cannot be excluded that mitochondria suffer functional injury, e.g . by the assembly of a mitochondria permeability transition pore.