THERAPEUTIC MANAGEMENT OF CEREBRAL ISCHEMIA

我们设计了一种与最常见的狒狒模型非常相似的模型 人类脑血管疾病的表现。利用我们独特的血管 封堵器，我们可以可逆地阻断大脑中动脉的血流 (MCA)。有了这个模型，我们就可以测试 各种治疗方法改变标准化治疗结果的可能性 缺血性侮辱。我们在拟议的漏斗期间的初步目标是 检查一个关键问题，即脑缺血是否会导致预后 在半急性或慢性期通过再灌注可以改善梗塞 在不增加发病率和死亡率的情况下进行进化。 微血管颅外-颅内(EC-IC)搭桥术现在是可行的 局灶性脑炎治疗的临床选择 缺血症。已经出现了多个病例报告，描述了 这种血管重建术后的慢性神经功能障碍。 这些报告表明，神经元有可能保留在临床上。 虽然在功能上沉默了很长一段时间，但仍然可行 脑血管中的闭塞区域。Astrup等人将这一区域命名为 存活但沉默的神经元被称为“缺血半暗带”。如果关键区域对 神经功能位于这个半影区内，然后增加血液 心流应该会改善神经学结果。因为增加的风险 脑梗死区的脑水肿，最早是神经外科医生 会尝试显微手术血运重建的时间是10天， 大多数人倾向于将这一程序推迟6周。使用我们的 灵长类动物模型我们计划阻断30只动物的大脑中动脉：EC-IC搭桥术将 两组分别于闭塞后10天和6周进行检查 (10只/组)。神经病学和神经病理学评分结果 这两组人将与一系列10个对照组的人进行比较 而不进行血管重建。如果缺血半暗带存在并且属于任何 临床意义，那么这些组之间的差异应该是 很明显。 在该方案的第二阶段，我们计划评估三种疗法 在急性局灶性脑损伤的治疗中具有潜在的益处 缺血：1)钙拮抗剂尼莫地平，2)高容量血症 使用右旋糖酐-40进行血液稀释，以及3)使用氟化钠-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MCA 遮挡。神经学和神经病理学评估将进行比较。 而对照组的结果是在两周后。

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.