Peripheral macrophages and T-cells accumulate in the degenerating optic tract after repetitive head impact.

Chronic white matter inflammation is a feature of traumatic brain injury (TBI), consistently observed in rodent models of repetitive mild TBI and persistnat in human TBI patients for years post-injury. We use a high-frequency head impact model (HFHI, 5 impacts per day, over 6 consecutive days) to investigate neuroimmune responses in the optic tract, a white matter region particularly vulnerable to injury-induced degeneration in mouse repeat mild TBI models. We integrated immunohistochemistry, digital spatial proteomics, transcriptomic profiling, and blood-brain barrier (BBB) assessments with non-invasive imaging modalities, including diffusion tensor imaging (DTI) and functional MRI (fMRI) to capture a comprehensive view of pathology. HFHI resulted in a sustained inflammatory response within the optic tract, marked by elevated IBA1