Excitotoxic lesions of the paraventricular hypothalamus: metabolic and cardiac effects.
The excitotoxin, N-methyl-D-aspartic acid (NMDA), was used to lesion cell bodies, but not fibers-of-passage, in the paraventricular hypothalamus. Bilateral injections of NMDA (12.6 nmol/100 nl) were made into the paraventricular hypothalamus in halothane-anesthetized male Sprague-Dawley rats. Water intake, food intake, urine output and body weight were measured daily for 26 days after lesioning. Lesioned rats exhibited a modest, but significant, reduction in the rate of gain of body weight, which was most closely correlated with decreases in food intake. Water intake and urine output were not significantly different among the groups. Resting blood pressure, heart rate and baroreflex sensitivity (using the infusion of phenylephrine method) were similar in conscious animals of both groups, 4-5 weeks after lesioning. Neuronal loss, primarily of parvocellular elements, was evident in the paraventricular hypothalamus and neuronal loss frequently extended into the ventro-medial thalamus adjacent to the paraventricular hypothalamus in NMDA-lesioned rats. In a second experiment, injections of NMDA were given acutely into the paraventricular hypothalamus of halothane-anesthetized rats. Upon recovery from anesthesia, behavioral excitation and increases in blood pressure and heart rate were evident for 1-2 hr. Histological examination of hearts taken 48 hr after injection of NMDA revealed a largely mononuclear inflammatory infiltration, hyperemia and myocardial hemorrhage and focal myocardial necrosis. Inflammatory and degenerative changes were most prominent in the left ventricular subendocardium. The cardiomyopathy possessed similarities with catecholamine-induced myocardial necrosis. The results indicated that NMDA-induced lesions of parvocellular elements of the paraventricular hypothalamus did not cause hyperphagia or obesity or alter the resting systemic circulatory function. However, an inflammatory cardiomyopathy, termed "excitotoxin-induced myocardial necrosis", was associated with injections of NMDA into the hypothalamus. Excitotoxin-induced myocardial necrosis may complicate any hemodynamic studies performed in rats in which lesions of the CNS have been produced by means of application of excitotoxins.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
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Rockhold
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Acuff
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Clower
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D001794:Blood Pressure; D001835:Body Weight; D001921:Brain / Q000473:pathology; D002319:Cardiovascular System / Q000503:physiopathology*; D006339:Heart Rate; D006706:Homeostasis; D008297:Male; D009206:Myocardium / Q000473:pathology; D016202:N-Methylaspartate; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000473:pathology; D011311:Pressoreceptors / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D001224:Aspartic Acid; D016202:N-Methylaspartate