Objective:

To determine the response of individual cell types in the choroid plexus to traumatic brain injury (TBI) using single-cell transcriptomics in the controlled cortical impact (CCI) mouse model.

Background:

Acute inflammation after TBI is a complex, multi-factorial process thought to drive secondary injury and worsen long-term prognosis. The choroid plexus plays a critical role in the recruitment of immune cells in the brain and produces secreted products like cerebrospinal fluid. The response of the choroid plexus in TBI is poorly understood but may have important implications for immunomodulatory treatments in the future. We sought to define the choroid plexus response to injury at a single-cell level using transcriptomic approaches.

Design/Methods:

Mice underwent controlled cortical impact (CCI) (n=3) or sham surgery (n=2). Each lateral ventricle choroid plexus was isolated at 24-hours post CCI and pooled by hemisphere and group. A single cell suspension was prepared, sequenced on the 10X platform, and analyzed using Seurat.

Results:

We identified 14,834 high quality cells across ipsilateral CCI, contralateral CCI, ipsilateral sham, and contralateral sham samples. Relative cell populations were similar across samples, except for lymphocytes and neutrophils, which trended towards higher representation in the CCI ipsilateral sample. We found transcriptomic differences in the choroid plexus epithelial cells of ipsilateral CCI tissue compared to other control groups. Differential gene expression analysis of the epithelial cell subset demonstrated that the most upregulated genes in the choroid plexus epithelium after CCI are CHIL1, A2M, and PCSK2, which may implicate changes in protease activity and regulation and tissue remodeling in injured tissue.

Conclusions:

Choroid plexus epithelial cells in ipsilateral injured tissue demonstrated transcriptional differences from contralateral and sham controls. Bioinformatic analysis suggests that these changes may be related to tissue remodeling, protein processing, and other inflammatory processes. These results may elucidate targetable pathways that reduce secondary inflammatory injury in patients with TBI.