A THERAPEUTIC MODEL FOR CEREBRAL ISCHEMIA

约有200万人遭受创伤性脑损伤(TBI) 每年，在这些脑外伤患者中，超过90%的人有过 流向大脑的血液急剧波动(脑缺血)。人与人 动物研究表明，脑缺血会对大脑造成损害 最终可能导致细胞死亡的细胞(神经元)。学习和记忆 损伤是继脑部之后最常见的行为问题 缺血症。这项拟议研究的目标是确定环境 治疗可以改善脑组织的行为和解剖效应 并能促进神经元的再生。拟议的研究将 检查是否：1)环境疗法可以减轻脑内神经元的损伤 海马体(参与记忆处理的大脑区域，也是 最易受脑血流剧烈变化影响的区域) 缺血，2)环境疗法可以促进海马区的神经发生 (新神经元的形成)缺血损伤后，3)生长因子 调节成人大脑神经发生的可能机制，以及4)时机 对脑缺血后实施环境治疗的影响 对解剖学和行为学恢复程度的影响。一种形态学 群体和行为群体将在拟议的研究中使用，以优化 实验设计，并确保形态(解剖学)措施 不受行为测试的影响。成年大鼠将被指派接受 不是缺血就是假(对照)手术。在这些群体中，动物将被 分配到3种治疗条件中的一种：复杂的环境， 非运动组和体力活动组。此外，建筑群中的动物 环境和体力活动条件将随机分配给 接受早期(紧接缺血后)或延迟(四天) 缺血后)干预。动物将被安置在分配给他们的 术后14天内在环境中活动。大鼠被分配到较晚的时间 手术后，治疗将被成对地安置在标准的实验室笼子中， 在开始环境操纵之前。经过环境治疗后， 形态学组的动物将被实施安乐死。大脑会做好准备 使用电子显微镜、免疫细胞化学和 无偏见的体视学方法(物理和光学解剖)。森林里的动物 行为组在安乐死前在水迷宫中进行为期18天的测试。 将使用电子显微镜和物理解剖方法来评估 神经元损伤，而免疫细胞化学和光学解剖方法将 用于评估神经发生和生长因子的表达。数据来自 水迷宫将用于评估短期空间学习，长期空间学习 空间记忆和非空间学习。从护理的角度来看，结果 这项研究具有重要的临床意义，因为大多数幸存者的需求 颅脑损伤时往往需要持续的护理，同时使用医疗 服务可能是间歇性的。

Approximately 2 million people suffer traumatic brain injury (TBI) annually and of these TBI victims, greater than 90 percent have had episodes of dramatic fluctuations in blood flow to the brain (cerebral ischemia). Human and animal studies have shown that cerebral ischemia results in damage to brain cells (neurons) which can eventually lead to cell death. Learning and memory impairments are the most common behavioral problems seen following cerebral ischemia. The objective of the proposed study is to determine if environmental therapy can ameliorate the behavioral and anatomical effects of cerebral ischemia and promote the regeneration of neurons. The proposed study will examine if: 1) environmental therapy can mitigate the damage to neurons in the hippocampus (brain region involved in the processing of memories and also the most vulnerable region to dramatic changes in blood flow) caused by cerebral ischemia, 2) environmental therapy can promote neurogenesis in the hippocampus (formation of new neurons) after ischemic damage, 3) growth factors are possible mechanisms that mediate neurogenesis in the adult brain, and 4) timing of implementation of environmental therapy following cerebral ischemia has an influence on the degree of anatomical and behavioral recovery. A morphological group and a behavioral group will be used in the proposed study to optimize the experimental design and to ensure that morphological (anatomical) measures are not influenced by behavioral testing. Adult rats will be assigned to receive either ischemia or sham (control) surgery. Within these groups, animals will be assigned to either one of 3 therapeutic conditions: complex environment, inactive group, and physical activity. Furthermore, animals in the complex environment and physical activity conditions will be randomly assigned to receive either early (immediately following ischemia) or late (four days following ischemia) intervention. Animals will be housed in their assigned environment for 14 days following surgery. Rats assigned to late timing of therapy will be housed in pairs in standard laboratory cages after surgery and before starting environmental manipulation. After environmental therapy, the animals in the morphology group will be euthanized. The brains will be prepared for quantitative analysis using electron microscopy, immunocytochemistry and unbiased stereological methods (physical and optical dissector). Animals in the behavior group will be tested in the water maze for 18 days before euthanasia. Electron microscopy and the physical dissector method will be used to assess neuron damage while immunocytochemistry and the optical dissector method will be used to assess neurogenesis and expression of growth factors. Data from the water maze will be used to assess short-term spatial learning, long-term spatial memory, and nonspatial learning. From a nursing perspective, results from this study are important clinically because the needs of most survivors of brain injury often times are for continuous nursing, while use of medical services may be intermittent.