Kajita S, Ogawa N, Sato M
Epilepsia. 1987 May-Jun;28(3):228-33. doi: 10.1111/j.1528-1157.1987.tb04212.x.
Our previous finding that intracerebroventricular (i.c.v.) administration of both thyrotropin-releasing hormone (TRH) and its analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417), suppressed seizure development of amygdaloid (AM) kindling and kindled AM seizures leads to a new hypothesis that endogenous TRH may be an antiepileptic substance in the brain. In this study, we examined postictal chronological changes in both immunoreactive TRH (IR-TRH) and TRH receptor binding activity in discrete brain regions of AM-kindled rats to study the relationship of the brain TRH system to kindling-induced seizure susceptibility. AM-kindled rats were decapitated 30 min, 24 h, 48 h, 7 days, and 21 days after the last kindled convulsion. IR-TRH increased markedly in the AM/pyriform cortex and hippocampus 24 and 48 h after the last convulsion, and returned to the control (unstimulated, sham-operated) value within 3 weeks after the convulsions ended. In contrast, a significant increase in the striatal TRH binding sites was evident 24 h after the cessation of convulsions which lasted 21 days. A lasting change in the striatal TRH neural system may be related to kindling-induced seizure susceptibility.
我们之前的研究发现，脑室内（i.c.v.）注射促甲状腺激素释放激素（TRH）及其类似物γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺柠檬酸盐（DN-1417）可抑制杏仁核（AM）点燃和点燃后的AM癫痫发作的发展，这导致了一个新的假设，即内源性TRH可能是大脑中的一种抗癫痫物质。在本研究中，我们检测了AM点燃大鼠离散脑区中免疫反应性TRH（IR-TRH）和TRH受体结合活性的发作后时间变化，以研究脑TRH系统与点燃诱导的癫痫易感性之间的关系。在最后一次点燃惊厥后30分钟、24小时、48小时、7天和21天，将AM点燃大鼠断头。在最后一次惊厥后24小时和48小时，AM/梨状皮层和海马中的IR-TRH显著增加，并在惊厥结束后3周内恢复到对照（未刺激、假手术）值。相比之下，在持续21天的惊厥停止后24小时，纹状体TRH结合位点明显显著增加。纹状体TRH神经系统的持久变化可能与点燃诱导的癫痫易感性有关。
