Pharmacological treatment following experimental cerebral infarction: implications for understanding psychological symptoms of human stroke.

Middle cerebral artery ligation in the rat produces decreases in catecholamine concentrations at brain sites uninjured by ischemic damage and a transient increase in spontaneous horizontal activity. Development of this hyperactivity can be blocked by postoperative treatment with the antidepressant, desmethylimipramine, or by preoperative destruction of norepinephrine terminals with 6-hydroxydopamine. These results suggest that ischemic damage to the cerebral cortex which injures some axonal branches of elaborately arborizing catecholamine-containing neurons may alter the biochemical and functional state of the entire system in its intact collateral axons. Thus the concept of stroke as a local injury producing symptoms by local structure-function relationships is conceptually inadequate, and poststroke symptoms must be evaluated with these "whole brain" concepts in mind. We suggest that the poststroke symptoms of apathy and depression may represent emotional changes which result from pathophysiological processes in catecholamine neurons far from the site of the stroke.