GENE EXPRESSION-ENVIRONMENT LINK IN CEREBRAL ISCHEMIA

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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.