ABSTRACT
Mild traumatic brain injuries (mTBIs) trigger a neuroinflammatory response, which leads to perturbations in the levels of inflammatory cytokines, resulting in a distinctive profile. A systematic review and meta-analysis were conducted to synthesize data related to levels of inflammatory cytokines in patients with mTBI. The electronic databases EMBASE, MEDLINE, and PUBMED were searched from January 2014 to December 12, 2021. A total of 5,138 articles were screened using a systematic approach based on the PRISMA and R-AMSTAR guidelines. Of these articles, 174 were selected for full-text review and 26 were included in the final analysis. The results of this study demonstrate that within 24 hours, patients with mTBI have significantly higher levels of Interleukin-6 (IL-6), Interleukin-1 Receptor Antagonist (IL-1RA), and Interferon-γ (IFN-γ) in blood, compared to healthy controls in majority of the included studies. Similarly one week following the injury, patients with mTBI have higher circulatory levels of Monocyte Chemoattractant Protein-1/C-C Motif Chemokine Ligand 2 (MCP-1/CCL2), compared to healthy controls in majority of the included studies. The results of the meta-analysis also confirmed these findings by demonstrating significantly elevated blood levels of IL-6, MCP-1/CCL2, and Interleukin-1 beta (IL-1ß) in the mTBI population compared to healthy controls (p < 0.0001), particularly in the acute stages (<7 days). Furthermore, it was found that IL-6, Tumor Necrosis Factor-alpha (TNF-α), IL-1RA, IL-10, and MCP-1/CCL2 were associated with poor clinical outcomes following the mTBI. Finally, this research highlights the lack of consensus in the methodology of mTBI studies that measure inflammatory cytokines in the blood, and also provides direction for future mTBI research.
ABSTRACT
Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15-20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9-213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.
