Hypoxic-ischemic encephalopathy is a major cause of neonatal death and long-term disability globally. Subsequent inflammation after the brain injury has been identified to be an important factor for neurological outcomes. Most studies have focused on early immunological changes following cerebral ischemia, but this strategy excludes many children from therapy since they present too late. Our group was the first to find long-lasting inflammation with activated T cells in the brain parenchyma up to five months after cerebral hypoxic ischemia in rodents and that peripheral lymphocytes in animals exposed to a neonatal brain injury are proliferating in response to brain antigens several months later. However, the distribution to specific brain regions, the meninges, and the T-cell transcriptome are entirely unexplored. Recently the immune response in the adult meninges has been explored and this tissue has now been suggested to be an active participant in many processes in brain development, physiology, and pathology. The meninges have been proposed as infiltration routes for leukocytes into the brain and different cell types including CD4+ T cells have been reported in the leptomeninges. In this study, we aim to characterize the temporal, regional, and transcriptional pattern of T cell activation in the brain, meninges, spleen, and blood after hypoxic-ischemic (HI) injury in neonatal mice using single-cell RNA sequencing, spatial transcriptomics, and FACS. Our ultimate goal is to identify novel treatments to reduce the injury size and improve neurological outcomes by modulating the immune response.