DIAZEPAM EFFECTS ON RECOVERY OF FUNCTION

这个项目探讨了一种可能性， 在脑损伤后不久， 功能非常容易受到干扰。 作为脑损伤的模型， 大鼠将接受单侧前内侧皮质损伤，这产生了一个 精确量化的感觉不对称， 8天 一些动物将在术后每天暴露于 注射安定 在最近的研究中，我们发现， 从术后12小时开始，持续术后3周 完全破坏损伤引起的感觉不对称的恢复， 不确定的时期 可以排除镇静或共济失调，因为 行为的效率和速度（与对称性相反） 受损 停药后10周（ 在我们观察的持续时间内），未发生恢复。 我们还发现，如果 地西泮的初始注射在恢复发生后施用， 只有一个非常短暂的（或没有）不对称出现，即使剂量 慢性安定升高。 我们计划证实这些观察结果， 将测试持续时间延长至12个月或更长， 停止药物治疗方案，并确定是否有其他病变 其他脑损伤的症状也会受到同样的影响。 似乎 特别值得注意的是，在此之后， 脑损伤，其中恢复过程是脆弱的深刻， 也许是永久性的破坏 这场危机的开始和持续时间 期间，地西泮的最小有效剂量， 苯二氮卓类拮抗剂的联合给药，以及其他 恢复药物（包括GABA激动剂或其他药物， 抗惊厥特性通常用于临床治疗或预防 脑损伤后癫痫发作）是我们计划解决的问题之一。

This project explores the possibility that there is a critical period shortly following brain damage during which the mechanisms of recovery of function are highly vulnerable to disruption. As a model of brain damage, rats will receive unilateral antero-medial cortex lesions, which yield a precisely-quantified sensory asymmetry that reliably recovers within about 8 days. Some of the animals will be exposed postoperatively to daily injections of diazepam. In recent work we found that a diazepam regimen beginning at 12 hrs after surgery and continuing for 3 postoperative weeks completely disrupts recovery from the lesion-induced sensory asymmetry for an indefinite period. Sedation or ataxia could be ruled out because the efficiency and speed (as opposed to the symmetry) of behavior were not impaired. As long as 10 weeks after discontinuation of the drug (the duration of our observations), no recovery occurred. We also found that if the initial injection of diazepam is administered after recovery occurs, only a very transient (or no) asymmetry appears, even if the dose of chronic diazepam is raised. We plan to confirm these observations, to extend the duration of testing to 12 months or more after the discontinuation of the drug regimen, and to determine whether other lesions and other symptoms of brain damage are affected in the same way. It seems especially noteworthy that there may be a critical stage of events after brain damage in which the recovery process is vulnerable to profound, perhaps permanent, disruption. The onset and length of this critical period, the minimum effective dose of diazepam, the effects of co-administration of benzodiazepine antagonists, and the effects of other agents on recovery (including GABA agonists or other drugs with anti-convulsant properties commonly used clinically to treat or prevent seizures following brain damage) are among the questions we plan to address.