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Changes in Cerebral Blood Flow and Postsynaptic Muscarinic Cholinergic Activity in Rats with Bilateral Carotid Artery Ligation

Positron Medical Center, Hamamatsu Medical Center
Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita-City, Shizuoka, Japan

Correspondence: For correspondence or reprints contact: Yasuomi Ouchi, MD, PhD, Positron Medical Center, Hamamatsu Medical Center, 5000, Hirakuchi, Hamakita-City, Shizuoka 434, Japan.

ABSTRACT

Changes in both regional cerebral blood flow (rCBF) and postsynaptic muscarinic cholinergic activity in the rat brain were investigated after ligation of the common carotid arteries (CCAs) bilaterally with ¹⁵O-labeled water (H₂ ¹⁵O) and [¹¹C]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 k₃, the rate of binding of ¹¹C-NMPB, were measured, based on the autoradiographic method and the graphical plotting analysis, respectively. Results: The levels of rCBF in the frontal cortex of the ligated group were significantly lower than those in the cerebellum and those in sham group, after 7 days and 1 mo postoperation. Although the level of k₃ in the frontal cortex 7 days after operation was not altered, it decreased significantly after 1 mo in the ligated group. Neither cortical infarct nor cortical neuronal loss was observed histologically. Conclusion: Common carotid artery ligation in Wistar rats caused a prolonged cerebral hypoperfusion without degeneration of the cortical neurons and a later decline of postsynaptic cholinergic receptor activity. These findings suggest that the decline in the postsynaptic cholinergic activity that is associated with the prolonged reduction in the cerebral blood supply may reflect pathophysiology that is equivalent to the deterioration of cognitive function in patients with chronic cerebrovascular insufficiency.

Key Words: cerebral hypoperfusion • [carbon-11]N-methyl-4-piperidylbenzilate • carotid artery ligation • PET

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