Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury

Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injuries can lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this ensuing neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. We hypothesized that TBI would lead to long-term changes in the transcriptional profile of microglial pathways associated with the development of subsequent neurologic impairment.

Male C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to Quantiseq 3'-biased RNA sequencing at 7, 30, and 90 d after TBI. K-means clustering on 396 differentially expressed genes was performed, and gene ontology enrichment analysis was used to determine corresponding enriched processes.

Differentially expressed genes in microglia exhibited four main patterns of expression over the course of TBI. In particular, we identified four gene clusters which corresponded to the host defense response, synaptic plasticity, lipid remodeling, and membrane polarization.

Transcriptional profiling within individual populations of microglia after TBI remains a critical unmet research need within the field of TBI. This focused study identified several physiologic processes within microglia that may be associated with development of long-term neurologic impairment after TBI. These data demonstrate the capability of longitudinal transcriptional profiling to uncover potential cell-specific targets for the treatment of TBI.