Traumatic brain injury–induced alterations in peripheral immunity

Abstract

Background The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury. Methods C57Bl/6 mice underwent closed head injury via a weight drop technique (n=5) vs. sham injury (n=3) per time point. Blood, spleen, and thymus were collected and immune phenotype, cytokine expression, and antibody production were determined via flow cytometry and multiplex immunoassays at 1, 3, 7, 14, 30, and 60 days post injury. Results TBI results in acute and chronic changes in both the innate and adaptive immune response. TBI resulted in a striking loss of thymocytes as early as 3 days post-injury (2.1×107 TBI vs. 5.6×107 sham, p=0.001). Similarly, blood monocyte counts were markedly diminished as early as 24 hours post-TBI (372/dl TBI vs. 1359/dl sham, p=0.002) and remained suppressed throughout the first month post-injury. At 60 days post-injury monocytes were polarized towards an anti-inflammatory (M2) phenotype. TBI also resulted in diminished IL-12 expression from day 14 post-injury throughout the remainder of the observation period. Conclusion TBI results in temporal changes in both the peripheral and central immune systems culminating in an overall immune suppressed phenotype and anti-inflammatory milieu. Level of Evidence Level 1 prospective randomized controlled animal experiment.

Acute Traumatic Brain Injury Induces CD4⁺ and CD8⁺ T Cell Functional Impairment by Upregulating the Expression of PD-1 via the Activated Sympathetic Nervous System

“…However, it was thought that severe TBI has no influence on the biology of B cells, based on the evidence provided by several studies indicating that the number and frequency of B cells does not change after injury [8, 34, 36]. Consistent with these reports, our study showed that aTBI induced a decrease in CD3 + and CD8 + T cells, but not in CD19 + B cells.…”

Lack of chronic neuroinflammation in the absence of focal hemorrhage in a rat model of low-energy blast-induced TBI

“…L or R indicate left or right subregion, respectively. Hipp = Hippocampus, Amy = Amygdala, AC = Anterior cortex, PC = Posterior cortex has also been reported in a mouse model of closed head injury using a standardized weight-drop technique [45]. The lack of inflammation observed in our animals indicates that low-energy blast exposures (74.5 kPa) are not always sufficient to sustain chronic neuroinflammation.…”

Innate immune responses to trauma

“…An increase in circulating splenic lymphocytes (due to mobilization of immune cells) occurs that is associated with a compromised BBB and the development of splenic atrophy early after experimental TBI 153 , and beyond 30 days after TBI, a decrease in F4/80 + macrophages in the red pulpa and of Ly6C lo tissue macrophages has been observed 154 . TBI is also associated with a loss of thymus mass as a result of a reduction in lineage marker-negative populations and mature T cells that is associated overall with immunosuppressive features 154 .…”

“…TBI is also associated with a loss of thymus mass as a result of a reduction in lineage marker-negative populations and mature T cells that is associated overall with immunosuppressive features 154 .…”