Immunocytochemical evaluation of cellular changes in a mouse model of direct cranial blast and advanced chronic traumatic encephalopathy in human postmortem brains
DeWalt, Gloria Jessica
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Traumatic brain injury (TBI) is a serious public health concern. Although moderate and severe forms of TBI receive considerable attention, mild TBI accounts for the majority of all injuries. The first two aims of this work used a rodent model of mild blast to simulate primary injury (damage from the blast wave only). The first aim evaluated potential changes in interneurons containing the calcium-binding proteins calretinin or parvalbumin. In addition, morphological changes in astrocytes and microglia were assessed. Brains were analyzed 48 hours and one month following exposure to single or repeated blasts, with a focus on the hippocampus due to its integral role in learning and memory. Results showed significant region-specific alterations in microglia morphology 48 hours following blast. The absence of structural alterations in microglia one month following blast indicated that the regional hippocampal vulnerability may be transient. The second aim compared glial morphologies in the retina and brain (the lateral geniculate nucleus, superior colliculus, and visual cortex) 48 hours or one month following multiple blasts. Fiber degeneration has received considerable attention, however, less is known about the status of glia throughout the visual pathway following mild blasts. Although no structural alterations were detected, it is possible that alterations in glia occurred at a more acute time scale as changes in glia can be rapid and reversible. The final aim of this work focused on the immunocytochemical characterization of tau pathology in the visual cortices of human postmortem brains with advanced chronic traumatic encephalopathy (CTE). CTE is a devastating tauopathy associated with mild, repetitive TBIs. Although visual deficits are reported in CTE, the primary visual cortex is often spared. The main hypothesis under investigation was whether visual association areas would have tau pathology, despite sparing of primary visual cortex. In addition, a sub-class of interneurons containing parvalbumin was used to evaluate a potential cell-specific vulnerability. Results showed increased tau pathology in visual association areas in advanced CTE, that was largely absent from the primary visual cortex. There was no effect on parvalbumin positive interneurons. The results of this work provides valuable insight regarding potential cell-specific resistance to CTE pathology.