てんかん重積モデルに対するthyrotropin-releasing hormone（TRH）の作用

Effects of Thyrotropin-Releasing Hormone (TRH) on Status Epilepticus in Rats.

　ラットの左側扁桃核にdibutyryl-cAMP 200μgとEDTA 67.2ng（db-cAMP／EDTA）を注入し，てんかん重積状態を誘発した。db-cAMP／EDTA注入後30分に，thyrotropin-releasing homlone（TRH）3mg／kg（n＝9），25mg／kg（n＝5），50mg／kg（n＝5）を経静脈的に投与した。また，TRH 50μg（n＝9）の右側側脳室内投与についても検討した。TRHを経静脈的に投与すると，3mg／kgには明らかな効果はなかったが，25mg／kg，50mg／kgの高用量では発作波や発作症状が有意に増強した。また，50mg／kgでのみ発作波の有意な抑制が認められたが，この現象には発作波や発作症状の増強が必ず先行して認められた。TRH 50μgの脳室内投与によっても，発作波や発作症状が増強し，それに続いて発作波が抑制される傾向が観察された。以上の結果から，てんかん重積状態の治療を目的にTRHを経静脈的に投与することには慎重な配慮が求められよう。

Recent studies have demonstrated that intramus-cular administration of thyrotropin-releasing hor-mone (TRH) or its analogue improves various clinical aspects of intractable epilepsy such as Lennox-Gastaut syndrome, West syndrome, and myoclonus epilepsy. Other clinical studies reported efficient property of intravenous TRH against sta-tus epilepticus. However, it is also true that intra-venous TRH produces epileptic seizures in patients with epilepsy or organic brain damage. Thus, the utility of intravenous TRH for the treatment of status epilepticus seems to be equivocal. To further explore the problem in this regard, we examined the effect of TRH on limbic status epilepticus in rats.

Thirty-eight male Wistar rats weighing 180-220g were used. Status epilepticus was induced by intracerebral injection of a combination of 200 μg of dibutyryl-cAMP (db-cAMP) and 67.2ng of eth-ylenediaminetetraacetic acid (EDTA) into the amygdala (AM) through an implanted cannula. 30 min later, TRH or vehicle (distilled water ) was administered intravenously (i. v.) or intracere-broventricularly (i. c. v.).

Although 3 mg/kg of TRH (n=9), when injected i. v., did not alter the pattern of electroclinical ictal responses induced by db-cAMP/EDTA, 25 mg/kg (n=5) and 50 mg/kg (n=5) of TRH significantly exaggerated EEG and/or behavioral ictal seizures, beginning immediately after the injection and last-ing for more than 30 min. With 50 mg/kg of TRH, the exaggerated seizure patterns were followed by marked suppression of electroclinical seizures. 50 μg of i. c. v. TRH (n=5), like higher doses of i. v. TRH, caused a slight, but not a significant, build up of electroclinical ictal seizures, beginning immedi-ately after the injection and lasting for about 30 min. This feature was sometimes followed by sei-zure suppression.

Our results suggest that i. v. TRH should be carefully used in patients with status epilepticus.