Differential Gene Expression Associated with Meningeal Injury in Acute Mild Traumatic Brain Injury

Abstract

Injury to the meninges is not uncommon after traumatic brain injury (TBI), yet minimal research has been directed toward understanding the relevant biology. After a concussive event, the meninges are observed to abnormally enhance on post-contrast magnetic resonance imaging (MRI) in some patients, but not all. The aim of this work is to identify genes differentially expressed in patients with meningeal injury. Patients presenting to the emergency room with suspected TBI received a standard research MRI and blood draw within 48 h of injury. Two groups of patients were included: those with and without abnormal enhancement of the meninges on post-contrast MRI, both without other imaging findings. Groups were compared on microarray gene expression in peripheral blood samples using Affymetrix (Santa Clara, CA) and Partek Genomics Suite (Partek, Inc., St. Louis, MO) software (false discovery rate, <0.05). Forty patients were enrolled with a time from injury to MRI/blood draw of 16.8 h (interquartile range, 7.5-24.1). We observed 76 genes to be differentially expressed in patients with meningeal injury compared to those without, such as receptor for Fc fragment of IgA, multiple C2 domains, transmembrane 2, and G-protein-coupled receptor 27, which have been previously associated with initiating inflammatory mediators, phagocytosis, and other regulatory mechanisms. Post-contrast MRI is able to detect meningeal injury and has a unique biological signature observed through gene expression. These findings suggest that an acute inflammatory response occurs in response to injury to the meninges following a concussion.

Keywords: MRI; brain trauma; concussion; gene expression.

FIG. 1.

TMI⁺ versus TMI^– scans. Example of magnetic resonance imaging obtained from 2 paitents in the study, with and without evidence of TMI. Shown are the GRE which is sensitive to blood, and DWI which is sentitive to ischemia, and pre- and post contrast FLAIR used to detect TMI. Red arrows indicated abnormal enhancment of meningese seen on post-contrast FLAIR in the falx cerebri and along the anterior convexity of the frontal lobe. DWI, diffusion weighted image; FLAIR, fluid-attenuated inversion recovery; GRE, gradient recalled echo; TMI, traumatic meningeal injury.

FIG. 2.

Top four differentially expressed genes. Of the 76 genes found to be differentially expressed in the TMI⁺ group in comparison to the TMI^– group, four were above a 1.5-fold change. These genes have been previously associated with inflammatory mechanisms, phagocytosis, and other regulatory systems. These findings suggest that gene expression profiles may inform a diagnostic biomarker of TMI. TMI, traumatic meningeal injury.

FIG. 3.

Hierarchical cluster. A hierarchical cluster analysis was able to correctly predict 70% of patients TMI groupings based on their gene expression changes. This suggests that gene expression biomarkers have a utility that are diagnostic of TMI. TMI, traumatic meningeal injury.