DIAZEPAM EFFECTS ON RECOVERY OF FUNCTION

这个项目探讨了存在一个关键时期的可能性 脑损伤后不久，在此期间，脑损伤的恢复机制 功能极易受到干扰。作为脑损伤的模型， 大鼠将接受单侧前内侧皮质损伤，这将产生 精确量化的感觉不对称，可靠地在大约 8天。其中一些动物将在术后每日暴露于 注射安定。在最近的工作中，我们发现安定疗法 从术后12小时开始，持续3周 完全扰乱从损伤引起的感觉不对称的恢复 一个不确定的时期。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)不是 受伤了。停药后长达10周( 在我们观察到的持续时间内)，没有恢复。我们还发现，如果 首次注射安定是在恢复后进行的， 只有非常短暂(或没有)的不对称出现，即使剂量 慢性安定升高。我们计划证实这些观察结果，以 将测试期限延长至12个月或更长时间 停止用药方案，并确定是否有其他损害 大脑损伤的其他症状也会以同样的方式受到影响。似乎 特别值得注意的是，可能会有一个关键阶段的事件后 在脑损伤中，恢复过程容易受到严重的、 也许是永久性的，颠覆。这一危急时刻的开始和持续时间 期间，安定的最小有效剂量，影响 苯二氮类拮抗剂的联合给药及其他药物的作用 恢复药物(包括GABA激动剂或其他药物 临床上常用于治疗或预防的抗惊厥特性 大脑损伤后的癫痫发作)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.