CHANGES IN CEREBRAL BLOOD-FLOW AND POSTSYNAPTIC MUSCARINIC CHOLINERGIC ACTIVITY IN RATS WITH BILATERAL CAROTID-ARTERY LIGATION

Changes in both regional cerebral blood flow (rCBF) and postsynaptic m uscarinic cholinergic activity in the rat brain were investigated afte r ligation of the common carotid arteries (CCAs) bilaterally with O-15 -labeled water ((H2O)-O-15) and [C-11]N-methyl-4-piperidylbenzilate, a potent muscarinic receptor antagonist, Methods: PET was performed in the same Wistar rat, 7 days and 1 mo after the CCA ligation, Regional cerebral blood flow and the transfer coefficient k(3), the rate of bin ding of C-11-NMPB, were measured, based on the autoradiographic method and the graphical plotting analysis, respectively, Results: The level s of rCBF in the frontal cortex of the ligated group were significantl y lower than those in the cerebellum and those in sham group, after 7 days and 1 mo postoperation. Although the level of k(3) in the frontal cortex 7 days after operation was not altered, it decreased significa ntly after 1 mo in the ligated group, Neither cortical infarct nor cor tical neuronal loss was observed histologically. Conclusion: Common ca rotid artery ligation in Wistar rats caused a prolonged cerebral hypop erfusion without degeneration of the cortical neurons and a later decl ine of postsynaptic cholinergic receptor activity. These findings sugg est that the decline in the postsynaptic cholinergic activity that is associated with the prolonged reduction in the cerebral blood supply m ay reflect pathophysiology that is equivalent to the deterioration of cognitive function in patients with chronic cerebrovascular insufficie ncy.