Knoblach S M, Kubek M J
Program in Medical Neurobiology, Indiana University School of Medicine, USA.
Neuroscience. 1997 Jan;76(1):97-104. doi: 10.1016/s0306-4522(96)00362-4.
Endogenous thyrotropin-releasing hormone has been hypothesized to modulate seizure activity, possibly by subserving an anticonvulsant function in limbic brain. A specific and sensitive radioimmunoassay was utilized to quantitate thyrotropin-releasing hormone levels in dorsoventrally dissected hippocampal subregions after partially (an experimental paradigm of complex partial epilepsy) or fully kindled (repeated generalized) seizures, to define specific seizure-related limbic pathways that may contain thyrotropin-releasing hormone. Samples were taken from electrode controls and 1, 6, 24, 48 and 144 h after a fully kindled seizure or 24 h after the first occurrence of a stage 3-4 (partially kindled) seizure in rats. Thyrotropin-releasing hormone levels were below controls in all subregions taken 1 h after a fully kindled seizure. They resembled control values 6 h after seizure, were substantially elevated at 24 and 48 h, and then returned to control levels by 144h. Low thyrotropin-releasing hormone levels seen shortly after the seizure presumably indicate peptide depletion during the ictus. The higher levels seen at later times occurred during a postictal period coinciding with refraction to additional seizure-generating stimulation. These values probably reflect enhanced synthesis since the largest increases were seen in subregions (dentate gyrus, hilus/CA4, CA3) that contain perforant path terminals, and where previously observed intrinsic hippocampal thyrotropin-releasing hormone messenger RNA increases were seen. The thyrotropin-releasing hormone response was less robust in ventral hilus/CA4 and CA3 areas, leading to speculation that this smaller response could, in part, explain why the ventral (temporal) hippocampus may be more susceptible to seizure-induced damage. No changes in thyrotropin-releasing hormone were detected after partially kindled seizures, suggesting that thyrotropin-releasing hormone is not involved in epileptogenesis or its stereotypic motor behavior. The time-course and distribution of thyrotropin-releasing hormone elevations seen after a fully kindled (repeated generalized) seizure, and the lack of effect of partial kindling (complex partial seizure) are consistent with previous observations concerning postictal thyrotropin-releasing hormone messenger RNA expression. These neurochemical results support the hypothesis that endogenous thyrotropin-releasing hormone can serve an anticonvulsant neuromodulatory function in specific limbic pathways relevant to temporal lobe epilepsy.
内源性促甲状腺激素释放激素被认为可调节癫痫活动，可能是通过在边缘脑区发挥抗惊厥功能来实现。利用一种特异性和敏感性高的放射免疫分析法，对部分点燃（复杂部分性癫痫的实验范式）或完全点燃（反复全身性发作）癫痫后，从背腹方向解剖的海马亚区中的促甲状腺激素释放激素水平进行定量，以确定可能含有促甲状腺激素释放激素的特定癫痫相关边缘通路。样本取自电极对照组以及大鼠完全点燃癫痫后1、6、24、48和144小时，或首次出现3 - 4期（部分点燃）癫痫后24小时。完全点燃癫痫后1小时所取的所有亚区中，促甲状腺激素释放激素水平均低于对照组。癫痫发作6小时后其水平与对照组相似，在24和48小时显著升高，然后在144小时恢复到对照水平。癫痫发作后不久出现的低促甲状腺激素释放激素水平可能表明发作期肽的消耗。后期出现的较高水平发生在发作后期，此时对额外的癫痫发作刺激产生不应期。这些值可能反映了合成增强，因为在含有穿通路径终末的亚区（齿状回、海马门/CA4、CA3）中观察到最大的增加，并且之前也观察到海马内源性促甲状腺激素释放激素信使核糖核酸增加。腹侧海马门/CA4和CA3区的促甲状腺激素释放激素反应较弱，这引发了一种推测，即这种较小的反应可能部分解释了为什么腹侧（颞叶）海马可能更容易受到癫痫发作诱导的损伤。部分点燃癫痫后未检测到促甲状腺激素释放激素的变化，这表明促甲状腺激素释放激素不参与癫痫发生或其刻板运动行为。完全点燃（反复全身性发作）癫痫后促甲状腺激素释放激素升高的时间进程和分布，以及部分点燃（复杂部分性癫痫）无影响，与先前关于发作后促甲状腺激素释放激素信使核糖核酸表达的观察结果一致。这些神经化学结果支持了内源性促甲状腺激素释放激素可在与颞叶癫痫相关的特定边缘通路中发挥抗惊厥神经调节功能这一假说。
