Sardorbek Abduganiev

Introduction. A Traumatic Brain Injury (TBI) is a blow to the head or penetration injury that results in disruption of normal brain function. Severity of TBI can range from mild to severe, with a concussion being a common form of a mild TBI. TBI is seen in a wide range of demographics, ranging from children playing sports, adults playing football in NFL, military personnel in blast incidents, and those involved in auto collisions ³. We’re able to visualize the damage from TBI using MRI and PET imaging, but what happens at the neuronal level is that there’s damage to the axons, vasculature and glia following trauma to the head⁴. Secondary injury stems from the inflammation and swelling following TBI. BBB permeability, influenced by nAChRa7 receptors and TRPV channels, plays a big role in secondary injury. Methods. Mice, as well as Sprague and Wilstar rats, were used in the experiments^1,2. nAChRa7 knockout rats were used to test the effect of the receptor on the level of inflammatory molecules. Various TRPV4 inhibitors were injected to measure the their effects on brain edema. TBI was induced through controlled cortical impact and weight drop device. Evans Blue dye was used to measure permeability. Western blots and ELISA were used to measure levels of protein levels and cytokine levels, respectively.  Results. nAChRa7 receptors on macrophages can be stimulated to reduce the synthesis and release of these inflammatory molecules ¹ .This was shown in rats in which following the knock out the nAChRa7 receptor, levels of TNFa and IL-1B, as well as activated microglia and neutrophils, increased¹. TRPV channels, which control the osmotic pressure in the brain, were shown to be sensitized and upregulated following a TBI. There was less water content in the rat models if TRPV antagonists were used, such as RN-1734 and antisense oligonucleotides². Conclusions. Following a TBI, there are inflammatory molecules that are released into circulation. These molecules travel to the spleen and activate the macrophages, which release more inflammatory molecules that contribute to the breakdown of BBB. This shows the presence and stimulation of this receptor can decrease the inflammation and BBB breakdown. The studies on TRPV channels implied that with TRPV4 activation after TBI, a change in tight junction structure caused the BBB epithelial cells to lose their sealing properties and become more permeable, resulting in brain edema² .

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