GENE EXPRESSION-ENVIRONMENT LINK IN CEREBRAL ISCHEMIA

描述：(申请人提供)脑缺血(急剧减少 血液流向大脑)是创伤性脑损伤常见的情况， 中风和心脏骤停。据报道，一些基因被激活。 这些基因在影响脑缺血的过程中发挥作用 细胞存活和细胞死亡的过程。然而，目前还不清楚是如何 一种流程可以比另一种流程更容易升级。因此，拟议的目标是 研究是为了确定环境刺激是否可以调节基因 在脑缺血中可见的表达并促进细胞存活 对侮辱的认知和感觉运动效果的改善。本研究 我将研究：1)环境刺激是否可以调节被激活的基因 在脑缺血中并可能促进细胞存活，2)环境 刺激可以影响将基因加工成蛋白质(蛋白质携带 规范行为的信息)，3)性别差异存在于基因和 脑缺血后的蛋白表达，以及4)细胞存活 环境刺激伴随着认知和认知能力的改善 感觉运动功能。成年雄性和雌性Wistar大鼠将获得 缺血或假(对照)手术。然后动物将被分配到其中的任何一个 4个条件：复杂的环境、运动学习、锻炼和社交 条件组(对照组)在脑缺血恢复后2d。老鼠 将在他们指定的环境中居住10天。分子， 组织学和行为组将在研究中用于优化 实验设计。经过环境刺激后，这些动物在 分子群将被安乐死，大脑将被分析基因 而组织学组中的动物将被安乐死和 将对大脑进行蛋白质表达分析。基因表达将被确定 通过原位杂交、免疫细胞化学和光学显微镜 方法将用于评估蛋白质的表达。行为中的动物 安乐死前将对患者进行认知和感觉运动功能测试。 将使用攀绳和旋转杆测试感觉运动功能 认知功能测试将使用水迷宫进行测试。从一个 从护理的角度来看，这项研究的结果在临床上很重要，因为 记忆力丧失是最常见和最持久的认知障碍 从脑缺血，并经常阻碍患者的进展在 康复。此外，缺血后出现的感觉运动障碍 损害可能会影响这些幸存者的长期结果。

DESCRIPTION: (provided by applicant) Cerebral ischemia (drastic reduction in blood flow to the brain) is common condition seen in traumatic brain injury, stroke, and cardiac arrest. It has been reported that some genes are activated in cerebral ischemia and that these genes play a role in influencing the processes of both cell survival and cell death. However, it is not clear how one process can be promoted over the other. Thus, the objective of the proposed study is to determine whether environmental stimulation can modulate the gene expression seen in cerebral ischemia and promote cell survival accompanied by amelioration in the cognitive and sensory motor effects of insult. This study will examine if; 1) environmental stimulation can modulate the genes activated in cerebral ischemia and possibly promote cell survival, 2) environmental stimulation can influence the processing of genes into proteins (proteins carry the message that regulates behavior), 3) gender differences exist in gene and protein expression after cerebral ischemia, and 4) cell survival following environmental stimulation is accompanied by improvement in cognitive and sensory motor functions. Adult male and female Wistar rats will receive either ischemia or sham (control) surgery. Then animals will be assigned to either one of 4 conditions: complex environment, motor learning, exercise, and social condition (control) group 2 days after recovery from cerebral ischemia. Rats will be housed in their assigned environment for 10 days. Molecular, histological, and behavior groups will be used in the study to optimize the experimental design. After environmental stimulation, the animals in the molecular group with be euthanized and the brains will be analyzed of gene expression while animals in the histological group will be euthanized and the brains will analyzed for protein expression. Gene expression will be determined by in site hybridization while immunocytochemistry and the optical dissector method will be used to assess protein expression. Animals in the behavioral group will be tested in cognitive and sensory motor function before euthanasia. Sensory motor function will be tested using rope climbing and rotating rode tests while cognitive function will be tested using the water maze. From a nursing perspective, results from this study are important clinically because memory loss is the most frequent and enduring cognitive disability resulting from cerebral ischemia and often hinders the patient's progress during rehabilitation. Additionally, the sensory motor deficit seen following ischemic damage can affect the long-term outcome of these survivors.