Objective:

To describe the choroid plexus response to traumatic brain injury (TBI).

Background:

Neuroinflammation is a critical component of secondary injury after TBI. Evidence suggests that the choroid plexus is a key site for immune recruitment to the brain, but little is known about its response to TBI.

Design/Methods:

Mice underwent controlled cortical impact (CCI) or sham surgery. Each lateral ventricle choroid plexus was isolated at 3, 6, or 24-hours post CCI in biological triplicate, for next generation sequencing and analyzed using DESeq2. Samples from an independent animal cohort were isolated 24 hours after injury for immunohistochemistry. 

Results:

The choroid plexus transcriptome revealed a biphasic, pro-inflammatory response to injury, with Gene Ontology categorizations “inflammatory response”, “immune response”, and “cellular response to lipopolysaccharide” as the most significant terms. Six hours after CCI, neutrophil chemoattractants Cxcl1 and Cxcl2 (fold change 1.3⋅103 and 7.9⋅104, respectively) and transcription factors Fos, Jun, and Egr1 were the most upregulated genes in the ipsilateral choroid plexus. Twenty-four hours post-CCI, Mmp3, Mmp12, and Lcn2, genes encoding matrix metalloproteases and metalloprotease-associated proteins, were among the most upregulated genes. Immunohistochemistry validated these findings with a large increase in neutrophils in the ipsilateral choroid plexus 24 hours after CCI. Upregulated genes at 24 hours post-CCI were notably enriched in targets of JUNB and FOSL2, which were themselves upregulated by3 hours after injury suggesting potential feed-forward regulation.

Conclusions:

The choroid plexus exhibits a biphasic, time-dependent transcriptomic response in the first 24 hours after TBI. Bioinformatic analysis suggests chemoattractants and key transcription factors are expressed in the first 6 hours after injury which recruit neutrophils to the choroid plexus. At 24 hours after injury, expression switches to metalloproteases that may be involved in permeabilizing the blood-CSF-barrier. These results may inform a strategy to target neutrophil entry into the brain through the choroid plexus to limit neuroinflammation after TBI.