A THERAPEUTIC MODEL FOR CEREBRAL ISCHEMIA

脑缺血的治疗模型

• 批准号: 6393084
• 负责人: TERESITA L BRIONES
• 金额: $ 26.53万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393084
• 关键词: behavior test; brain injury; cerebral ischemia /hypoxia; disease /disorder model; electron microscopy; environmental therapy; hippocampus; immunocytochemistry; laboratory rat; morphology; nerve growth factors; nervous system regeneration; neurogenesis; neurotrophic factors; nonhuman therapy evaluation; trauma

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.

大约有200万人遭受创伤性脑损伤（TBI） 在这些TBI受害者中，超过90%的人有过 流向大脑的血流剧烈波动（脑缺血）。人力和 动物研究表明，脑缺血导致脑损伤， 细胞（神经元），最终可能导致细胞死亡。学习记忆 损伤是脑损伤后最常见的行为问题， 缺血这项研究的目的是确定环境 治疗可以改善大脑的行为和解剖效应， 促进神经元再生。拟定的研究将 检查是否：1）环境疗法可以减轻对神经元的损伤， 海马体（大脑中参与记忆处理的区域， 最易受血液流动剧烈变化影响的区域） 环境治疗可促进海马神经发生 缺血性损伤后（新神经元的形成），3）生长因子 可能的机制，介导神经发生在成年人的大脑，和4）时间 脑缺血后环境治疗的实施， 对解剖和行为恢复程度的影响。形态学 组和行为组将用于拟议的研究，以优化 实验设计，并确保形态学（解剖学）措施， 不受行为测试的影响。成年大鼠将被分配接受 缺血或假手术（对照）。在这些群体中，动物将 分配给3种治疗条件之一：复杂环境， 不活跃组和体力活动。此外，综合体中的动物 环境和体力活动条件将被随机分配到 接受早期（缺血后立即）或晚期（4天 局部缺血后）干预。动物将饲养在其指定的 手术后14天。大鼠被分配至延迟给药时间 手术后，治疗组将成对饲养在标准实验室笼中， 然后开始环境操纵。经过环境治疗后， 对形态学组中的动物实施安乐死。大脑会准备好 用于使用电子显微镜、免疫细胞化学和 无偏体视学方法（物理和光学解剖）。动物 行为组在安乐死前在水迷宫中测试18天。 电子显微镜和物理解剖方法将用于评估 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。的数据 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 从这项研究是重要的临床，因为大多数幸存者的需要， 脑损伤经常需要持续护理，而使用医疗 服务可能是间歇性的。