THERAPEUTIC MANAGEMENT OF CEREBRAL ISCHEMIA

我们设计了一个狒狒模型， 人类脑血管疾病的表现。 利用我们独特的血管 封堵器，我们可以可逆地阻塞大脑中动脉的血流， (MCA)没有麻醉的狒狒 通过这个模型，我们可以测试 各种疗法改变标准化治疗结果的潜力 缺血性损伤 我们在拟议的欢乐期内的初步目标是 研究缺血性心脏病是否会导致 在半急性期或慢性期再灌注可改善梗死 而不增加发病率和死亡率。 微血管颅外-颅内（EC-IC）搭桥术现在是一种可行的 治疗局灶性脑梗死患者的临床选择 缺血 出现了多个病例报告，描述了 这种血管重建手术后的慢性神经功能缺损。 这些报告表明，神经元有可能在临床上 存活，但在远端长时间功能沉默， 脑血管中的闭塞区域。 Astrup等人将这一区域称为 存活但沉默的神经元的"缺血半暗带"。"如果关键领域 神经功能位于这个半影内，然后增加血液 血流应该能改善神经功能。 由于风险增加， 脑水肿在梗死区，最早，大多数神经外科医生 将尝试显微手术血运重建是在10天， 大多数人倾向于将这一程序推迟6周。 使用我们 我们计划在30只动物中闭塞MCA的灵长类动物模型：EC-IC旁路将 分别于术后10天和6周进行 (10动物/组）。 结果？神经学和神经病理学评分 将这两组与10组对照组进行比较 不进行血管重建 如果存在缺血半暗带并且属于任何类型 临床意义，那么这些组之间的差异应该是 很明显 在本方案的第二阶段，我们计划评估三种疗法 在治疗急性局灶性脑梗死中具有潜在益处 缺血：1）钙拮抗剂尼莫地平，2）高血容量 用右旋糖酐-40血液稀释，和3）使用Fluosol-DA。这些疗法 将在我们的灵长类动物模型中进行评估，包括6小时和永久性MCA 闭塞 将比较神经学和神经病理学评价 两周后的对照组的结果。

We have designed a baboon model which closely parallels the most common manifestations of human cerebrovascular disease. Using our unique vascular occluder, we can reversibly obstruct flow in the middle cerebral artery (MCA) of the unanesthetized baboon. With this model we are able to test the potential of various therapies to alter the outcome of a standardized ischemic insult. Our initial goal during the proposed funneling period is to examine the critical question of whether outcome from ischemic infarction can be improved by reperfusion in the semiacute or chronic stage of evolution without increasing morbidity and mortality. Microvascular extracranial-intracranial (EC-IC) bypass is now a viable clinical option in the treatment of patients suffering from focal cerebral ischemia. Multiple case reports have appeared describing the reversal of chronic neurologic deficits following such revascularization procedures. These reports suggest that it is possible for neurons to remain clinically viable although functionally silent for prolonged periods distal to the area of occlusion in a cerebral vessel. Astrup et al have termed this area of viable but silent neurons the "ischemic penumbra." If areas critical to neurologic function are located within this penumbra, then increasing blood flow should improve neurologic outcome. Because of the risks of increasing cerebral edema in the area of infarct, the earliest that most neurosurgeons would attempt microsurgical revascularization is at 10 days, with the majority preferring to delay such a procedure for 6 weeks. Using our primate model we plan to occlude the MCA in 30 animals: EC-IC bypass will then be carried out at 10 days and 6 weeks after occlusion in two groups (10 animals/group). Results of?neurologic and neuropathologic scores in these two groups will be compared with those in a series of 10 controls without revascularization. If the ischemic penumbra exists and is of any clinical significance, then a difference among these groups should be apparent. In the second stage of this protocol we plan to evaluate three therapies with a potential benefit in the treatment of acute focal cerebral ischemia: 1) the calcium antagonist nimodipine, 2) hypervolemic hemodilution with Dextran-40, and 3) use of Fluosol-DA. These therapies will be evaluated in our primate model with both six hour and permanent MCA occlusion. Neurologic and neuropathologic evaluations will be compared with the results in controls at two weeks.