Sports-Related Concussions Result in Reduced Expression of Inflammatory Cytokines
Background: SRCs are common in athletes and can result in neurological symptoms and long-lasting deficits; however, there is a great degree of heterogeneity in recovery and outcome. To better determine mechanisms related to recovery, we examined gene expression changes prior to and during the acute and sub-acute periods following a SRC in a sample of athletes who reported a good recovery.
Methods: Using a prospective design, blood samples were collected from 256 collegiate contact sport athletes prior to the start of the sports season (baseline); in the 15 athletes who subsequently sustained a SRC, blood samples were obtained within 6 hours of injury (acute) and at 7 days (sub-acute) post-injury. Within subject differential expression of whole genome analyses was determined by comparing acute and sub-acute transcriptome profiles obtained from microarray data using the Partek Genomics Suite analysis program.
Results: Of the 174 genes that were differentially expressed at either time point compared to pre-season samples, 97.7% were shared among both time points. Reduced expression was observed in 159 genes, and over-expression was found in 17 genes. Genes with the greatest magnitude of down-regulation were inflammatory-related and included IL-8, which was reduced by -6.94-fold in the acute and -13.80-fold in the sub-acute period, and chemokine (C-X-C motif) ligand 2 (CXCL2), which had fold changes of -4.67 and -7.71 in the acute and sub-acute periods, respectively. Although the expressions changes in general was reduced from the acute to the sub-acute period, 22 genes out of 159 down-regulated genes were up-regulated to a higher degree during the sub-acute period, including the CD69 molecule, which changed from -5.28 to -3.34, and interferon gamma (INF-g), which changed from -3.49 to -2.53. One of the more prominently up-regulated genes was the chemokine (C-C motif) receptor 2 (CCR2), with fold changes of 2.88 and 1.90 in the acute and sub-acute periods, respectively.
Implications: Our findings suggest that recovery from a SRC is associated with modulation of inflammation through cytokine and chemokine gene-pathways. Future work is required to identify individual variability in recovery from SRC, which can contribute to development of personalized therapeutic agents.