CALCIUM BLOCKER AND RELATED THERAPY FOR STROKE RECOVERY

这个项目的目标是研究活动和 药物治疗对术后远期组织学和功能预后的影响 实验性卒中大鼠为制定合理的 康复策略和优化神经保护治疗。 中风后会有实质性的恢复，这是可以修改的 通过第一次体力活动和服药 在伊克图斯之后的几周。强迫过度使用或停用受影响的 前肢会增加梗塞面积，减少新的神经元 皮质中的连接，并阻止前肢运动的恢复 活动。正常钙稳态和生长发育障碍 因子反应性炎症和DNA片段化 缺血区可能共同产生延迟神经元。 因过度使用或停用而死亡和功能受损 对侧的前肢。改变电机的模式 干预(康复)和各种药物疗法可能 增强或延缓这些细胞过程，从而恢复 取决于它们何时启动或持续多长时间 在恢复期仍在继续。 使用一个表征良好的局灶性缺血损伤模型， 再灌流加重(“再灌流损伤”模型)，我们将 属性来测试强制过度使用或停用的效果 梗死灶的对侧或同侧前肢 缺血损伤后前两周。我们将测量 用定量方法研究过度使用或废弃对长期恢复的影响 前肢位置和脑梗塞体积。这些结果将是 与生长因子表达、炎症反应的关系 (NFkB)、细胞凋亡(TUNEL)和神经元丢失的定量 (体视学)在缺血区的组织标本中。我们 将测试我们修改这些事件并提高恢复的能力 通过改变造型范例，从而模拟不同的 康复策略，并通过改变发病时间和 神经保护性药物治疗的持续时间。

The goal of this project is to study the influence of activity and pharmacotherapy on long-term histologic and functional outcome after experimental stroke in rats in order to develop a rational rehabilitation strategy and to optimize neuroprotective therapy. Substantial recovery occurs after stroke and this is modifiable by physical activity and drug administration during the first weeks after ictus. Forced overuse or disuse of the affected forelimb will increase infarct size, reduce new neuronal connections in cortex, and prevent recovery of forelimb motor activity. Impairment of normal calcium homeostasis and growth factor response inflammation, and DNA fragmentation in and around the ischemic region may conspire to produce delayed neuronal death and impaired function in response to overuse or disuse of the contralateral forelimb. Varying the pattern of motor intervention (rehabilitation) and various pharmacotherapies may enhance or retard these cellular processes and hence recovery depending upon when they are started or how long they are continued during the recovery period. Using a well-characterized model of focal ischemic damage that is aggravated by reperfusion ("reperfusion injury" model), we will test the effect of forced overuse or disuse by casting the forelimb contralateral or ipsilateral to the infarct during the first two weeks after ischemic insult. We will measure the effect of overuse or disuse on long-term recovery by quantitating forelimb placement and infarct volume. These results will be correlated with expression of growth factor (bFGF), inflammation (NFkB), apoptosis (TUNEL), and quantitation of neuronal loss (stereology) in histologic samples from the ischemic region. We will test our ability to modify these events and improve recovery by altering the casting paradigm thereby simulating different rehabilitation strategies, and by altering the time of onset and the duration of neuroprotective pharmacotherapy.