Rockhold R W, Acuff C G, Clower B R
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Neuropharmacology. 1990 Jul;29(7):663-73. doi: 10.1016/0028-3908(90)90028-p.
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.
兴奋性毒素N-甲基-D-天冬氨酸（NMDA）被用于损毁下丘脑室旁核的细胞体，而非传导束纤维。在氟烷麻醉的雄性Sprague-Dawley大鼠的下丘脑室旁核进行双侧NMDA注射（12.6纳摩尔/100纳升）。损毁后26天内每天测量水摄入量、食物摄入量、尿量和体重。损毁大鼠的体重增加速率出现适度但显著的降低，这与食物摄入量的减少最为密切相关。各组之间的水摄入量和尿量没有显著差异。在损毁后4 - 5周，两组清醒动物的静息血压、心率和压力感受性反射敏感性（采用去氧肾上腺素输注法）相似。在NMDA损毁的大鼠中，下丘脑室旁核出现神经元丢失，主要是小细胞成分，并且神经元丢失常常延伸至下丘脑室旁核附近的腹内侧丘脑。在第二个实验中，对氟烷麻醉的大鼠的下丘脑室旁核进行急性NMDA注射。从麻醉中恢复后，行为兴奋以及血压和心率升高持续1 - 2小时。注射NMDA 48小时后取出心脏进行组织学检查，结果显示主要为单核细胞炎性浸润、充血、心肌出血和局灶性心肌坏死。炎症和退行性改变在左心室心内膜下最为明显。这种心肌病与儿茶酚胺诱导的心肌坏死有相似之处。结果表明，NMDA诱导的下丘脑室旁核小细胞成分损毁不会导致食欲亢进或肥胖，也不会改变静息时的全身循环功能。然而，一种被称为“兴奋性毒素诱导的心肌坏死”的炎性心肌病与向下丘脑注射NMDA有关。兴奋性毒素诱导的心肌坏死可能会使在通过应用兴奋性毒素造成中枢神经系统损毁的大鼠中进行的任何血流动力学研究变得复杂。
