MECHANISMS OF KINDLED SEIZURE SUPPRESSION BY CYSTEAMINE

半胱胺已被证明可以抑制点燃的癫痫发作，剂量从90 毫克/公斤至300毫克/公斤，当点燃的大鼠到阶段V。这个项目将 包括仔细评估脑部化学变化和 为了更好地了解癫痫发作的发作抑制情况 半胱胺的作用机制。 本项目的目的是通过以下方式更好地了解这些机制 半胱胺可以消除癫痫发作。点燃和假冒的大鼠 手术后将接受一次腹膜腔注射 半胱胺(200 mg/kg)。在给药后， 将观察动物的行为变化和癫痫发作 压制。这些老鼠将在已知的时间间隔内被扑杀 半胱胺注射，大脑被移除，皮质，小脑， 将解剖中脑、桥脑和海马体。这些组织 将被提取并评估多肽、氨基酸、受体和 儿茶酚胺水平。化学变化与环境变化的相关性 癫痫抑制可能允许识别一种化学变化 随着癫痫发作活动的减少。研究的下一步将是 确定该化合物的拮抗剂是否也会抑制癫痫发作。 目前我们实验室和其他实验室的研究表明， 半胱胺导致生长抑素和去甲肾上腺素减少 行政管理。 半胱胺实验的结果表明： 给药时，对癫痫的抑制作用并不是发生在 生长抑素最低的点，但在一个点上， 生长抑素最接近对照水平。这些观察结果 建议在给药后抑制癫痫发作 这种药物可能是由于受体的重新增敏，而不是由于受体减少 生长抑素本身。研究表明，儿童死亡率的下降 生长抑素与癫痫发作的阻断密切相关，它的增加 与癫痫发作的复发相似。这些观察结果表明， 生长抑素水平的改变可能起到治疗作用 癫痫发作。

Cysteamine has been shown to suppress kindled seizures at doses from 90 mg/kg to 300 mg/kg when given to rats kindled to stage V. This project will involve the careful evaluation of the alterations in brain chemistry and the onset of the suppression of seizures in order to better understand the mechanism of action of cysteamine. The aims of the present project are to better understand the mechanisms by which cysteamine eliminates seizures. Rats which are kindled and sham operated will receive a single intraperitoneal injection of cysteamine(200mg/kg). Following the administration of the drug, the animals will be observed for behavioral changes as well as seizure suppression. The rats will be killed at known time intervals following cysteamine administration, the brain removed, and the cortex, cerebellum, midbrain, ponsmedulla, and hippocampus will be dissected. These tissues will be extracted and evaluated for peptide, amino acid, receptor, and catecholamine levels. The correlation of the chemical changes to the seizure suppression may allow the identification of one chemical alteration with a decrease in seizure activity. The next step in the study will be to determine if antagonists of the compound will also suppress seizures. Studies at present from our laboratory as well as others show that both somatostatin and norepinephrine are decreased as a result of cysteamine administration. The results of the cysteamine experiments have shown that following administration of the drug, the suppression of seizures occurs not at the point where somatostatin is the lowest, but at a point where the levels of somatostatin are the closest to the control levels. These observations suggest that the suppression of the seizures following administration of the drug may be due to a receptor resensitization rather than the decrease of the somatostatin itself. Studies have shown that the decrease of somatostatin closely parallels the block of seizures, and its increase parallels the return of seizures. These observations suggest that the alteration in the levels of somatostatin may play a therapeutic role in seizures.