Yamamoto M, Tamura A, Kirino T, Shimizu-Sasamata M, Sano K
Central Research Laboratories, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Eur J Pharmacol. 1991 May 17;197(2-3):117-23. doi: 10.1016/0014-2999(91)90509-o.
The effects of thyrotropin releasing hormone (TRH) on behavioral and histological changes were studied in rats subjected to left middle cerebral artery occlusion. The drug was given i.p. once or several times a day from 1 week after occlusion for 2 weeks. A single administration of TRH (1 and 10 mg/kg) did not affect the neurological deficits, but recovery of the deficits was accelerated by multiple administration (7 times a day) of TRH and single administration (once a day) of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH analogue with a longer half-life. Both YM-14673 and single (1 and 10 mg/kg) and multiple administration of TRH ameliorated the disturbance of passive avoidance learning. Neuronal degeneration in the cerebral cortex and striatum was not influenced by the administration of TRH. Thus, we found that neurological deficits and disturbance of passive avoidance learning behavior in middle cerebral artery-occluded rats could be ameliorated by administration of TRH.
在大脑中动脉闭塞的大鼠中研究了促甲状腺激素释放激素（TRH）对行为和组织学变化的影响。自闭塞后1周起，每天经腹腔注射该药物1次或数次，持续2周。单次注射TRH（1和10mg/kg）不影响神经功能缺损，但多次注射TRH（每天7次）和单次注射YM-14673（Nα-[[(S)-4-氧代-2-氮杂环丁烷基]羰基]-L-组氨酰-L-脯氨酰胺二水合物），一种半衰期更长的新型TRH类似物（每天1次）可加速神经功能缺损的恢复。YM-14673以及单次（1和10mg/kg）和多次注射TRH均改善了被动回避学习的障碍。TRH给药对大脑皮质和纹状体中的神经元变性没有影响。因此，我们发现，给予TRH可改善大脑中动脉闭塞大鼠的神经功能缺损和被动回避学习行为障碍。
