Effect of Middle Cerebral Artery Occlusion on Catecholamine Metabolism in Rat Brain

Abstract

The authors previously reported on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) in rats 1 hour after the occlusion of the left middle cerebral artery. It was found that LCGU was decreased in the ipsilateral cerebral cortex and the lateral striatum, where the LCBF was also reduced. On the other hand, LCGU was increased in the ipsilateral medial striatum, olfactory tubercle, globus pallidus, subthalamic nucleus, and lateral habenula, which are the “non-ischemic” regions and closely connected with the dopaminergic neurons. In the present work, catecholamines and their metabolites were measured using the same ischemic model rats. The results were compared with the changes in LCGU and LCBF in the various cerebral regions. Noradrenaline concentration was reduced mainly in the “ischemic” regions, such as the ipsilateral cerebral cortex and lateral striatum, and there was an increase in the “non-ischemic” lateral thalamic nucleus. On the other hand, dopamine (DA) was increased bilaterally in the regions closely connected with dopaminergic neurons. However, 3, 4-dihydroxyphenylacetic acid and homovanillic acid were increased only in the ipsilateral regions and a small decrease was found in the contralateral striatum. These changes in DA and its metabolites indicate that DA metabolism was increased ipsilaterally in both the “ischemic” and “non-ischemic” regions but it was probably inhibited on the contralateral side. Since DA agonist, apomorphine, has been reported to increase energy metabolism (LCGU) mainly in the regions closely connected with the dopaminergic neurons, the results of the present work suggest that the ischemia in the ipsilateral cortex and lateral striatum caused an increase in DA neuron activity, which may be the cause of the increased LCGU in the ipsilateral “non-ischemic” dopamine rich regions, whereas the decrease in LCGU, inspite of the increased DA metabolism in the ipsilateral cortex and lateral striatum, were probably due to the direct effects of ischemia (the depletion of glucose supply). The contralateral change in DA was thought to be a biochemical diaschisis, which was mediated neuronally via a crossed nigrostriatal pathway.