Novel pharmaceutical combination confers protection from delayed cell death following transient cerebral ischemia
Chapman, Courtney Myfanwy.
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Stroke 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.