Pediatric Repetitive Mild Traumatic Brain Injury Elicits T Cell-Mediated Neuroinflammation

Pediatric repetitive mild traumatic brain injury (rmTBI) is a major public health concern with links to chronic cognitive dysfunction. Neuroinflammation represents a significant maladaptive outcome after rmTBI. Persistent innate and adaptive immune cell responses can lead to neurodegeneration and deficits in brain development. Therefore, a deeper understanding of the early dynamics of peripheral immune cell infiltration after pediatric rmTBI is critical for the development of effective treatment. We hypothesize that pediatric rmTBI alters neuroinflammation through T cell infiltration. We used wild-type (C57BL/6) and T cell knockout (TCRβ^-/- δ^-/-) mice to test this hypothesis. We developed a pediatric postnatal day 21 rmTBI model, with three consecutive subconcussive impact acceleration injuries separated in time by 1 week. After inducing rmTBI in juvenile mice, we observed a progressive infiltration of macrophages, CD8⁺, and CD4⁺ T cells into the brain parenchyma, which increased with repeated injury. Furthermore, neuroinflammation in the white matter was detected when we analyzed the lateral corpus callosum (CC). Since increased infiltration of CD4⁺ and CD8⁺ T cells was detected, we utilized TCRβ^-/- δ^-/- mice to further explore the role of T cells on neuroinflammation after pediatric rmTBI. We observed a reduction in the infiltration of pro-inflammatory macrophages and decreased neuroinflammation in the lateral CC. Overall, our findings highlight the significant role of T cell infiltration in the modulation of neuroinflammation following rmTBI in the developing brain, suggesting that they may serve as potential therapeutic targets for managing neuroinflammation following pediatric brain injuries.