Infiltrating Monocytes Attenuate The Neuroinflammatory Response After Traumatic Brain Injury
Young Chun, Miles Gilliam, William Fulton, Chhinder Sodhi, David Hackam, *Isam Nasr
Johns Hopkins, Baltimore, MD
Background (issue): TBI induces a robust neuroinflammatory response that activates the innate immune system. The interplay between the microglia and the infiltrating monocytes can attenuate the neuroimmune response.
Methods: A murine controlled cortical impact TBI model was used. Three experimental groups: (1)wild-type (WT) control, (2)WT, (3)CX3CR1GFP mice were used. Cell sorting was used to isolate monocytes and microglial cells from the brain. Real-time PCR quantified cytokine gene expression. Statistical analysis: Student's T-test and One-way ANOVA.
Findings: CX3CR1 positive monocytes were identified in the spleen on post-injury day (PID) 7 (n=5) but not on PID 1 (n=5). On PID 1, the infiltrating monocytes had significantly higher gene expression of the anti-inflammatory gene IL-10 (31.66±5.013, n=5) but decreased expression of the pro-inflammatory gene TNFɑ (512.5±59.35, n=5) compared to the expression in brain microglia: IL-10 (2.748±0.3728, n=5), and TNFɑ (1220±166.8, n=5). On PID 7, the infiltrating monocytes had higher gene expression of the anti-inflammatory gene IL-10 (7.068±1.79, n=4) but decreased expression of the pro-inflammatory genes IL-6 (8.898±0.7059, n=5) and TNFɑ (92.64±20.07, n=4) compared to the expression in brain microglia: IL-10 (1.604±0.4127, n=5), IL-6 (85.68±12.82, n=5), and TNFɑ (512.6±80.31, n=5).
Conclusions (implications for practice): Our findings demonstrate that infiltrating monocytes play a key role in both the early and the delayed immune response of TBI pathogenesis. Infiltrating monocytes displayed an anti-inflammatory gene expression profile in the injured brain on PID 1 and PID 7. These infiltrating monocytes express anti-inflammatory cytokines that may improve outcomes after traumatic brain injury.
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