Widespread and cell-type-specific transcriptomic reorganization following mild traumatic brain injury.

Abstract

Knowledge of how traumatic brain injury (TBI) alters the brain is urgently needed. A major challenge to this understanding is that TBI is a multiscale problem capable of evoking a host of perturbations across the brain and often presents large subject-to-subject variability. To circumvent these challenges, here, we employ the murine closed-head impact model of engineered rotational acceleration (CHIMERA) TBI model to produce mild, diffuse TBI reproducibly across mice in the subacute phase and apply spatial transcriptomics to study the multiscale effects of TBI. In doing so, we identify generalizable signatures of TBI that are present across brain regions, as well as a variety of brain-region- and cell-type-specific dysregulation. This dysregulation includes unexpected susceptibility of astrocytes in the molecular layer of the dentate gyrus, as well as dramatic gene expression changes in neurons of the thalamus. Ultimately, our work here helps to distill the multiscale complexity of TBI into interpretable brain regions, cell types, and molecular sequelae.