Date of Award
Doctor of Philosophy
The mechanisms mediating neuronal recovery and cardiovascular complications after ischemic stroke are not completely known. In these investigations, I examined changes in neuropeptides and a catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), following middle cerebral artery occlusion (MCAO) in adult male Wistar rats.;Five days following MCAO, the immunoreactivity for TH and neuropeptide Y (NPY) increased in the insular cortex (IC) within the peri-infarct zone. NPY also increased ipsilaterally in the basolateral nucleus of the amygdala, whereas leucine-enkephalin, dynorphin and neurotensin increased ipsilaterally in the central nucleus of the amygdala. Sham MCAO was ineffective.;Neurochemical changes were assessed 5 days after localized excitotoxic lesion of the IC or primary somatosensory cortex (SSC-I). Damage to the IC but not SSC-I reproduced the ipsilateral neurochemical changes of MCAO. Nevertheless, damage to the SSC-I produced local increases in NPY. Saline injection was ineffective.;The time-course of these changes was studied to understand the possible mechanisms for these neurochemical changes. The cortical NPY increase became significant at 1 day, maximal at 3-5 days, and subsiding by 10 days after MCAO. The amygdalar changes followed a similar time-course with peaks at 3-5 days and complete recovery by 10 days.;MCAO with intracerebroventricular injection of colchicine demonstrated that cortical neurons were responsible for the local NPY increase and that ipsilateral transmission of signals from the ischemic IC to the amygdala was involved in producing the amygdalar neurochemical changes.;The role of cortical NPY increase as an endogenous neuroprotective response to stroke was investigated using antisense oligodeoxynucleotide specific for NPY-Y1 receptors. A reduction in Y1 binding sites within the IC produced a doubling of the infarctolume following MCAO.;The possibility that these neurochemical changes mediate cardiovascular complications of stroke was investigated by comparing the cardiovascular responses to stress at different time after MCAO or sham MCAO. MCAO exaggerated the cardiovascular responses to stress in a time-course comparable to that of the amygdalar neurochemical changes.;Thus, my results clearly showed specific neurochemical changes in the peri-infarct zone and the ipsilateral amygdala. I also provided evidence to implicate these changes in neuroprotection and cardiac consequences of stroke.
Cheung, Raymond Tak, "Neurochemical Changes Following Stroke: Role In Neuroprotection And Cardiac Susceptibility" (1996). Digitized Theses. 2687.