SEIZURES, ANTICONVULSANTS AND RECOVERY FROM BRAIN DAMAGE

癫痫发作、抗惊厥药和脑损伤的恢复

• 批准号: 2268551
• 负责人: THERESA D HERNANDEZ
• 金额: $ 9.29万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2268551
• 关键词: GABA receptor; amygdala; animal tissue; anticonvulsants; behavior disorders; benzodiazepine receptor; brain injury; diazepam; disease /disorder model; disease /disorder prevention /control; drug adverse effect; electrophysiology; epilepsy; experimental brain lesion; frontal lobe /cortex; gamma aminobutyrate; generalized seizures; glutamate receptor; histology; kindling; laboratory rat; neuropharmacology; neurophysiology; neuropsychology; partial seizure; phenobarbital; phenytoin; receptor sensitivity; serotonin receptor; statistics /biometry; GABA receptor; amygdala; animal tissue; anticonvulsants; behavior disorders; benzodiazepine receptor; brain injury; diazepam; disease /disorder model; disease /disorder prevention /control; drug adverse effect; electrophysiology; epilepsy; experimental brain lesion; frontal lobe /cortex; gamma aminobutyrate; generalized seizures; glutamate receptor; histology; kindling; laboratory rat; neuropharmacology; neurophysiology; neuropsychology; partial seizure; phenobarbital; phenytoin; receptor sensitivity; serotonin receptor; statistics /biometry

Seizures frequently accompany brain injury. However, the incidence and persistence of post-traumatic seizures depend greatly upon the site and nature of the damage. It is widely accepted that seizures occurring after brain damage are detrimental to recovery because they increase the risk of post-traumatic epilepsy and when severe enough, can cause neuronal damage in and of themselves. Consequently, anticonvulsants are commonly administered in an effort to prevent the occurrence of seizures after brain injury. Yet, only a few clinical studies have systematically investigated the effects of this anti-convulsant prophylaxis on recovery from the behavioral deficits produced by the brain damage. Indeed, the focus of the majority of the studies has been to determine the success with which anti- convulsants prevent pot-traumatic seizures, per se, and not the impact of this procedure on recovery of function. Findings from a recent clinical study, as well as studies using animals, suggest that the use of anti- convulsants following brain damage may not be beneficial for behavioral recovery, and may, indeed, be detrimental. Moreover, there are some data in the animal literature to suggest that mild, infrequent seizures following brain damage may facilitate behavioral recovery. Because of the importance of these issues, whether or not preventing post-traumatic seizures with anti-convulsants is truly beneficial to recovery from behavioral deficits, the following research plan is proposed: (a) systematically determine the effect of experimentally-induced ("kindled") seizures on recovery of somatosensory function following cortex damage, (b) determine if preventing those seizures with anti-convulsants (including diazepam, phenobarbital and phenytoin) alters this outcome, and (c) determine the impact of each of these manipulations on postsynaptic receptor sensitivity as measured electrophysiologically. Results from these studies should provide information as to the mechanisms by which post-traumatic seizures and anti-convulsant administration affect behavioral recovery and, perhaps, suggest ways to minimize the degree of deficit following brain injury, while at the same time decreasing the likelihood of post-traumatic epilepsy.

癫痫发作经常伴随着脑损伤。 但是，发生率和 创伤后癫痫发作的持久性在很大程度上取决于现场， 损害的性质。 人们普遍认为，癫痫发作发生 脑损伤对恢复有害，因为它们增加了 创伤后癫痫病，如果足够严重，可能会造成神经元损害 本身。 因此，抗惊厥药通常是 为防止大脑后的癫痫发作而进行管理 受伤。 然而，只有少数临床研究系统地研究了 这种抗惊动预防的影响对从 大脑损伤产生的行为缺陷。 确实，关注 大多数研究都是为了确定抗 抽搐者可以防止盆栽癫痫发作，本身，而不是 此过程有关恢复功能的过程。 最近的临床发现 研究以及使用动物的研究表明，使用抗 脑损伤后的抽搐药可能对行为不利 恢复，实际上可能是有害的。 此外，还有一些数据 在动物文献中暗示温和，不经常癫痫发作 脑损伤后可能有助于行为恢复。 因为 这些问题的重要性，无论是否阻止创伤后 具有抗惊厥药的癫痫发作确实有益于从中恢复 行为缺陷，提出了以下研究计划：（a） 系统地确定实验诱导的效果（“点燃”） 在皮质损伤后恢复体感功能的癫痫发作，（b） 确定是否防止抗惊厥药的癫痫发作（包括 地西ep，苯巴比妥和苯妥英，改变了这种结果，（c） 确定每种操纵对突触后的影响 受体敏感性是在电生理上测量的。 结果 这些研究应提供有关其机制的信息 创伤后癫痫发作和抗惊厥施用影响 行为恢复，也许提出了最小化程度的方法 脑损伤后的赤字，同时减少 创伤后癫痫的可能性。