Mishra P K, Burger R L, Bettendorf A F, Browning R A, Jobe P C
Department of Basic Sciences, University of Illinois College of Medicine at Peoria 61611.
Exp Neurol. 1994 Jan;125(1):58-64. doi: 10.1006/exnr.1994.1006.
The role of norepinephrine in regulating brainstem seizures has been well documented. These seizures are characterized by running/bouncing clonus and tonic extensor convulsions. Evidence for noradrenergic regulation of brainstem seizures comes partially from studies with genetic models of epilepsy which are characterized by innate noradrenergic deficits and from selective lesioning of noradrenergic neurons and/or pathways. The present study was conducted to evaluate whether destruction of the noradrenergic system using DSP4 (N-(2-chloroethyl)-N-2-bromobenzylamine) influences forebrain seizure severity. Accordingly, 90 female Sprague-Dawley rats (49-55 days old) received DSP4 (50 mg/kg ip) after a pretreatment of desipramine (a norepinephrine reuptake inhibitor), fluoxetine (a serotonin reuptake inhibitor), or saline. A control group of 30 animals received two administrations of saline. Three weeks later, these animals were tested for facial and forelimb clonus (FFC) threshold (convulsive current50; CC50) via corneal electroshock stimulation. The FFC CC50 thresholds in the animals treated with saline plus DSP4 were significantly reduced compared to control (vehicle-vehicle) values. Also, desipramine pretreatment, which partially protected the noradrenergic system from the neurotoxicity of DSP4, completely obviated the reduction in FFC thresholds. A subsequent evaluation of brainstem seizure response using maximal electroshock through earclip electrodes confirmed the noradrenergic influence on brainstem seizure regulation. These observations provide additional support for a noradrenergic role in forebrain as well as brainstem seizure regulation.
去甲肾上腺素在调节脑干癫痫发作中的作用已有充分记载。这些癫痫发作的特征为奔跑/跳动性阵挛和强直性伸展性惊厥。去甲肾上腺素能对脑干癫痫发作进行调节的证据部分来自对癫痫遗传模型的研究，这些模型的特征是先天性去甲肾上腺素能缺陷，也来自对去甲肾上腺素能神经元和/或神经通路的选择性损伤。本研究旨在评估使用DSP4（N-(2-氯乙基)-N-2-溴苄胺）破坏去甲肾上腺素能系统是否会影响前脑癫痫发作的严重程度。因此，90只雌性Sprague-Dawley大鼠（49 - 55日龄）在接受地昔帕明（一种去甲肾上腺素再摄取抑制剂）、氟西汀（一种5-羟色胺再摄取抑制剂）或生理盐水预处理后，接受DSP4（50 mg/kg腹腔注射）。30只动物的对照组接受两次生理盐水注射。三周后，通过角膜电休克刺激测试这些动物的面部和前肢阵挛（FFC）阈值（惊厥电流50；CC50）。与对照组（载体-载体）值相比，生理盐水加DSP4处理的动物的FFC CC50阈值显著降低。此外，地昔帕明预处理部分保护了去甲肾上腺素能系统免受DSP4的神经毒性，完全消除了FFC阈值的降低。随后使用通过耳夹电极的最大电休克对脑干癫痫发作反应进行评估，证实了去甲肾上腺素能对脑干癫痫发作调节的影响。这些观察结果为去甲肾上腺素能在前脑以及脑干癫痫发作调节中的作用提供了额外支持。
