Chronic traumatic brain injury induces neurodegeneration, neuroinflammation, and cognitive deficits in a T cell-dependent manner

Abstract

Traumatic brain injury (TBI) can lead to chronic neuroinflammation, and neurodegeneration associated with long-term cognitive deficits. Following TBI, the acute neuroinflammatory response involves microglial activation and the release of proinflammatory cytokines and chemokines which induce the recruitment of peripheral immune cells such as monocytes and ultimately T cells. Persistent innate and adaptive immune cell responses can lead to chronic neurodegeneration and functional deficits. Therefore, understanding the dynamic interaction between chronic immune responses and TBI-related pathogenesis and progression of the disease is crucial. We hypothesized that T cells have an essential role in TBI severity and recovery. We used generic T cell deletion mice (TCRβ^−/−δ^−/−) vs Wild-type mice that underwent controlled cortical impact assessing behavioral, histological, and immune system response outcomes at 3 months post-TBI. The absence of T cells reduced neurodegeneration and was associated with improved neurological outcomes 3 months post-injury. Furthermore, the absence of T cells enhanced an anti-inflammatory phenotype in peripheral myeloid cells in the injured brain. Collectively, these data indicate that T cells promote persistent neuropathology and functional impairments chronically after TBI.