Adult Mouse Controlled Cortical Impact Visium Spatial Transcriptomics

Here we investigated the topographical relationship of early transcriptional responses to a single, focal TBI in mice by controlled cortical impact (CCI). Guided by the presence of the anterior commissure (AC) in coronal sections at the rostro-caudal point of impact, we compared gene expression changes in the neocortex (CTX) and corpus callosum-external capsule (CC-EC), striatum (STR) and AC. Injury-induced gene expression changes were detected in the CTX, CC-EC and STR but not AC and were principally segregated based on cytoarchitecture, and secondarily by proximity to the site of impact. Additionally, unbiased spatial clustering revealed a positive relationship between proximity to the impact and the number of acutely differentially expressed genes within the laminar CTX. Next, we examined the effects of systemic depletion of neutrophils and monocytes on spatial gene expression changes in the injured brain. Overall design: Visium (10X Genomics) spatial transcriptiomics prolfiling of the contused left hemisphere of the forebrains of mice given a single controlled cortical impact (CCI). Coronal sections at the focal point of contusion (at the level of the anterior commissure) were profiled from 15-20 weeks-old C57BL/6J mice given a CCI or Sham surgery (no craniectomy or impact). Experiment 1: CCI versus Sham mice at 2 days post-injury (DPI) and 7 DPI. Experiment 2: CCI mice treated with anti-GR-1 antibodies (to deplete circulating neutrophils and monocytes) versus CCI mice treated with control antibodies at 2 DPI and 7 DPI.