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Item Behavioral covariation in the treatment of chronic pain(Montana State University - Bozeman, College of Letters & Science, 1986) Kalsher, Michael JohnItem Object and spatial recognition in the ischemic gerbil(Montana State University - Bozeman, College of Letters & Science, 2010) Clement, Bridget Williams; Chairperson, Graduate Committee: A. Michael BabcockThe Mongolian gerbil is extensively used to model transient cerebral ischemia, a type of stroke that can occur with anoxia and cardiac arrest. A global ischemic insult in the gerbil produces damage to hippocampal CA1 pyramidal cells comparable to that observed in humans. A limited number of models are available to evaluate the behavioral consequences of cerebral ischemia in the gerbil. The goal of the present experiments was to evaluate the impact of transient cerebral ischemia on object and spatial recognition memory as these tasks have not been previously utilized with the gerbil model. Following ischemic insult (5-min bilateral carotid occlusion) or sham procedure, gerbils were tested in a familiar environment with novel objects. A familiarization phase followed by separate test phases for presentations of a novel object or object location were conducted. Exploratory behavior for the novel object or object location was evaluated using an automated tracking system. Results indicated that both ischemic and sham subjects were able to recognize the novel object when placed in the environment. However, when confronted with a familiar object, placed in a novel location, neither group exhibited a significant increase in exploratory behavior. A second experiment was conducted to further investigate the spatial recognition task. Subjects were habituated to the apparatus in addition to the experimental objects. Under this experimental condition, both groups exhibited significant exploratory behavior for the object placed in the novel location. The ischemic and control groups differed from each other during habituation with ischemic subject showing significantly higher activity levels. It is possible that differences between the groups remain but that these recognition findings are a result of extended habituation to the experimental objects. Further investigation of this matter is needed to determine the effect of prior object exposure on exploratory behavior in the spatial recognition task.Item Novel pharmaceutical combination confers protection from delayed cell death following transient cerebral ischemia(Montana State University - Bozeman, College of Letters & Science, 2009) Chapman, Courtney Myfanwy; Chairperson, Graduate Committee: A. Michael BabcockStroke is a leading cause of death and disability throughout the world; ischemia is the most common form of stroke. Medical procedures such as cardio-pulmonary bypass surgery can cause ischemic stroke can be caused. There are no treatments to limit neural impairment following stroke. The current research investigates neuroprotection offered by treatment with a novel drug combination consisting of Simvastatin TM, Gemfibrozil TM, Troglitazone TM, and Spironolactone TM. Animals were treated with the drug cocktail three weeks proceeding and one week subsequent to surgery. Ischemic insult was induced by clamping the carotid arteries for 5 min. Sham subjects underwent similar surgical procedures, but the carotids were not clamped. Twenty-four hrs following the surgical procedure locomotor activity was monitored in an open field for 5 min. Seven to fourteen days following ischemia or the sham procedure animals were sacrificed and sections containing the hippocampal CA1 region were mounted on slides and stained with cresyl violet. The CA1 region was rated on a 4-point scale for level of damage. Rodents generally show increased locomotor activity following transient global ischemia in an open field. In our study, ischemic animals that received vehicle demonstrated increased activity relative to the animals that received the drug treatment on all behavioral measures. Ischemic animals that received vehicle treatment had significantly more neural damage in the hippocampal CA1 region than ischemic animals receiving the drug. The appearance of neurons in the CA1 hippocampal regions of animals in the sham condition was not significantly different from ischemic animals in the drug treatment condition. It is concluded that the drug treatment is effective in offering neuroprotection during transient global ischemia. The next step is to characterize the biochemical mechanisms behind the neuroprotection conferred by the drug treatment. Contrasting the protein expression levels of animals receiving the vehicle treatment with animals receiving the drug treatment following an ischemic insult will assist in elucidating these pathways. Predictions are made regarding the biochemical mechanisms affected by the drug treatment based on previous research on the biochemical pathways affected by each pharmaceutical.