CHOLINESTERASE INHIBITION IMPROVES BLOOD-FLOW IN THE ISCHEMIC CEREBRAL-CORTEX

The ability of central cholinesterase inhibition to improve cerebral b lood flow in the ischemic brain was tested in Sprague-Dawley rats with tandem occlusion of left middle cerebral and common carotid arteries. Cerebral blood flow was measured with lodo-C-14-antipyrine autoradiog raphy in 170 regions of cerebral cortex, The regional distribution of blood flow was characterized in normal animals by cerebral blood flow maxima in the temporal regions. After 2 h ischemia, minimum cerebral b lood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemis phere in an area approximately symmetrical to the ischemic focus. Hept yl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most reg ions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in th e right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 re gions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions, The redistribution of cereb ral blood flow to the sensorimotor area of the right hemisphere of ani mals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine. Copyright (C) 1997 El sevier Science Inc.