Date of Award
Bachelor of Science (B.S.) in Biochemistry and University Honors
Diazepam -- Therapeutic use, GABA -- Agonists, Brain damage, Hippocampus (Brain), Cognitive neuroscience
Traumatic brain injury (TBI) induces an upregulation of neurogenesis in the brain specifically in the hippocampus, an area pertaining to learning and memory formation. Although this upregulated response is intuitively thought to be restorative, previous studies show that the nascent neurons generated after TBI exhibit abnormalities, such as aberrant morphologies and early migrations, which could suggest to be maladaptive. The GABA-A agonist diazepam has been shown to inhibit this upregulation in neurogenesis and normalizes dendrites after TBI. To determine whether this modulation of neurogenesis is ultimately beneficial or detrimental to cognitive recovery, diazepam was administered to C57BI/6J wild-type mice following a controlled cortical impact (CCI) injury for one week. Mice underwent the Morris Water Maze (MWM) and Reversal Morris Water Maze testing one month later to examine cognitive function in the absence of upregulated neurogenesis with diazepam. The mechanism in which diazepam inhibits post-TBI neurogenesis is also examined by quantifying the proliferative activity of hippocampal neural stem cells (NSCs) after CCI. Diazepam was found to rectify hippocampal-dependent memory after CCI in the MWM test but not in the reversal MWM test. The percent of proliferating hippocampal NSCs was not found to be significant in any experimental group. Therefore, proliferative activity of hippocampal neural stem cells was determined to not be affected by diazepam. Further studies are needed to determine the mechanism of diazepam and its effects on cognitive function after TBI using other behavioral tests.
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Doan, Van Khanh, "The Effect of Diazepam on Early Neural Stem Cells Proliferative Activity and Hippocampal-Dependent Memory after Traumatic Brain Injury" (2021). University Honors Theses. Paper 1097.