Dystrophic Functions of Aged Astrocytes Following Traumatic Brain Injury

This proposal will determine the role of astrocytes in the etiology of age-related pathological responses in a mouse model of traumatic brain injury (TBI). Recent epidemiological data show that age is a significant risk factor for acquired brain injury, which clinically, aged individuals have strikingly increased morbidity and mortality following TBI, compared to younger individuals. Those aged individuals that do survive the initial trauma suffer from decreased functional recovery as well. Recent data from human survivors of TBI, post-mortem tissue samples, as well as rodent studies have shown that neuroinflammation, as assessed by microglia/macrophage phenotype, is persistent for years after the initial injury. Importantly, dysregulated neuroinflammation is a consistent hallmark for virtually all neurodegenerative disease. The overall design of this project will delineate the contribution of astrocytes to the neuroinflammatory response at multiple time points spanning acute through chronic phases post injury. Further, we will be specifically targeting astrocytes using a novel vector-mediated regulator of function in an attempt to abrogate their dysfunctional response to TBI. Collectively, data generated from these studies will be leveraged to define a therapeutic treatment strategy to prevent the aberrant and dysregulated inflammatory response to TBI that is associated with aging.