Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex.
The ability of central cholinesterase inhibition to improve cerebral blood 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- 14C-antipyrine autoradiography 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 blood flow values were found in the lateral frontal and parietal areas on the left hemisphere, and a new maximum was found in the right hemisphere in an area approximately symmetrical to the ischemic focus. Heptyl-physostigmine (eptastigmine), a carbamate cholinesterase inhibitor with prolonged time of action improved cerebral blood flow in most regions, with the exception of the ischemic core. The drug also enhanced the ischemia-induced rostral shift of cerebral blood flow maxima in the right hemisphere. The effects of eptastigmine were more marked 24 h after ischemia. Discriminant analysis showed that data from only 22 regions was sufficient to achieve 100% accuracy in classifying all cases into the various experimental conditions. The redistribution of cerebral blood flow to the sensorimotor area of the right hemisphere of animals with cerebral ischemia, a phenomenon possibly related to recovery of function, was also enhanced by eptastigmine.
Scremin
O U
OU
West Los Angeles VA Medical Center, CA 90073, USA.
Li
M G
MG
Scremin
A M
AM
Jenden
D J
DJ
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine