REDUCED ACTIVITY OF THE PYRUVATE-DEHYDROGENASE COMPLEX BUT NOT CYTOCHROME-C-OXIDASE IS ASSOCIATED WITH NEURONAL LOSS IN THE STRIATUM FOLLOWING SHORT-TERM FOREBRAIN ISCHEMIA

Previous studies have identified changes in the activities of the pyru vate dehydrogenase complex (PDHC) and cytochrome c oxidase during earl y recirculation following short-term cerebral ischemia. However, the r elationship of these changes to the delayed selective neuronal loss th at develops as a result of short-term ischemia is incomplete,ly define d. The effects of ischemia and recirculation on the activities of thes e enzymes in the dorsolateral striatum, a region containing many susce ptible neurons, and the ischemia-resistant paramedian cortex have been compared. No significant loss of activity of cytochrome c oxidase was seen in either region during the first few hours of recirculation fol lowing 30 min of ischemia. A decrease (of 32%) was observed at 24 h in the dorsolateral striatum. However, this probably resulted from chang es in the mitochondrial fraction due to advanced neuronal degeneration . By contrast, there was a significant decrease (by 24%) in activity o f PDHC at 3 h following a 30-min, but not a 10-min, ischemic period. O nly the 30-min ischemic period resulted in extensive delayed neuronal loss. In the paramedian cortex, there was no significant change in PDH C and no neuronal loss following either ischemic period. These results provide strong evidence for a close association between neuronal loss and changes in the activity of PDHC but not cytochrome c oxidase in t he dorsolateral striatum. (C) 1997 Elsevier Science B.V.