Histologic analysis of cortical tissue from patients with post traumatic stress disorder and chronic traumatic encephalopathy
Ventrano, Victor Albert
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BACKGROUND: Mild Traumatic Brain Injury (mTBI) is increasingly recognized as an adverse health consequence for athletes who participate in contact sports, such as football or boxing, as well as military personnel who are exposed to concussive blasts during training and combat operations. A consequence of this repetitive brain injury can be the development of a number of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE), a disease involving the buildup of toxic phosphorylated tau (p-tau) in the pre-frontal cortical tissue. Additionally, it has been found that military personnel suffering repeated mTBI from primary blast concussions are prone to development of post traumatic stress disorder (PTSD), a disease that is becoming increasingly common among returning service members. Because mTBI is a common cause for both PTSD and CTE, it is possible for the two diseases to manifest comorbidly in an individual. Though much is known about PTSD psychologically and CTE neuropathologically, little is known about the overlapping effect of the two diseases together as well as PTSD neuropathologically. What is known, however, is that aquaporin-4; a channel involved in the movement of water through the blood brain barrier, is often affected by CTE and may play a role in PTSD as well. OBJECTIVE: The objective of this study was to primarily to analyze the disruption of aquaporin-4 around cerebral blood vessels due to chronic traumatic encephalopathy. A secondary objective of this project was to determine if any unique physiopathological biomarkers exist in PTSD and if the effects of CTE are exacerbated when present comorbidly with PTSD. METHODS: This study involved the analysis of multiple cohorts that had suffered from CTE, PTSD and CTE comorbidly, or neither disease as a control. In order to assess the primary objective, two cohorts, a CTE-only and a control, were analyzed to determine the effect of p-tau on aquaporin-4 directly around cerebral vessels in the pre-frontal cortex. The samples were cut from blocks and stained for the desired markers. Following staining, images were taken using a confocal microscope and the images were analyzed using Amaris and FIJI. For the secondary objective, samples were prepared in a similar way with three cohorts: CTE-only, CTE+PTSD comorbid, and a control. Images were obtained and processed in the same way. RESULTS: It was found that aquaporin-4 density is significantly reduced around both arterial and venous lesional vessels. Additionally, it was found that p-tau was more readily deposited in the depths of the sulci of the pre-frontal cortex due to the unique forces caused by repeated mTBI. However, PTSD was not found to significantly compound the disease when comorbidly present with CTE nor to have a unique biomarkers present. CONCLUSION: P-tau present in CTE causes a significant reduction in aquaporin-4 around cerebral vessels in the pre-frontal cortex, thereby potentially inhibiting the movement of fluids and clearance of metabolites into and out of the brain. Additionally, p-tau is more readily deposited in the depths of the sulci of the pre-frontal cortex. However, PTSD does not compound the CTE disease process when comorbidly present.