Alteration of muscarinic acetylcholine binding sites in the postischemic brain areas of the rat using in vitro autoradiography

Abstract

We studied the postischemic alteration of muscarinic acetylcholine binding sites in the rat brain using in vitro [ 3H]quinuclidinyl benzilate (QNB) autoradiography. Transient ischemia was induced by the occlusion of the middle cerebral artery (MCA) for 90 min and such occlusion followed by various recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3 days of recirculation, [ 3H]QNB binding sites were found to be significantly decreased in the cerebral cortex ( P < 0.01) and lateral segment of the caudate putamen ( P < 0.05), both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. Moreover, 3 days after the ischemia, significant decreases of [ 3H]QNB binding sites were observed in the ipsilateral thalamus and the amygdala, and also in the substantia nigra 1 week after the ischemia, areas which had not been directly affected by the original ischemic insult. This postischemic phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. These results indicate that alteration of muscarinic acetylcholine binding sites may be involved not only in the ischemic foci, but also in the exo-focal remote areas, in which delayed neuronal degeneration due to neuronal network disturbances after the ischemia was observed. We suggest that multifocal postischemic alterations of muscarinic acetylcholine binding sites may exacerbate the clinical symptoms of patients during the chronic stage of stroke.