Editors' ChoiceInflammation

The brain’s immune system hibernates in response to systemic injury

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Science Translational Medicine  05 Apr 2017:
Vol. 9, Issue 384, eaan2771
DOI: 10.1126/scitranslmed.aan2771

Abstract

In a small cohort of prostatectomy patients, systemic inflammation influenced the brain’s immune response and cognition.

The failure of the bench-to-bedside approach in treating acute brain injury can be partially attributed to the inherent differences in the complexity and diversity in physiology between humans and animal models. Experiments in surgical animal models have shown a close interplay between systemic surgical insult and the brain’s innate immune system. However, demonstrating similar phenomena in humans has been a challenge. The Forsberg et al. study uses a human clinical paradigm with robust pre- and post-surgical testing, analogous to an animal study, to illustrate the reaction of the brain's immune system to a systemic insult.

Eight patients undergoing surgical prostatectomy were studied before and 3 to 4 days after surgery with a battery of tests aimed at describing systemic and central immunologic changes. After robotic prostatectomy, patients had a global decrease of [11C]PBR28 binding to translocator protein in gray matter (a marker of microglial activity) by positron emission tomography, a decrease in lipopolysaccharide (LPS)–induced release of TNF-α in ex vivo blood cells, and an increase in systemic cytokine levels. The decrease in [11C]PBR28 binding was correlated with a decrease in immunoreactivity in peripheral blood cells. Additionally, [11C]PBR28 binding was associated with impairment in the Stroop color word interference test. Forsberg et al. concluded that after a systemic surgical insult, the brain reacts with a transient downregulation of its immune system. The transient immune suppression is associated with specific impairment in cognitive function. The authors present the hypothesis that immune suppression following surgery is a compensatory reaction to the initial “cytokine storm,” which was not detected in this study, as the systemic immune reaction is activated within minutes to hours after the initial insult.

The strength of the study is that it takes a small but uniform (only 8 patients) group and demonstrates a robust effect with brain metabolic, ex vivo immunological and cognitive correlates. The study puts into perspective the importance of systemic insults on brain physiology and function. The limitation of the study is the lack of information about what happens immediately after surgery. The brain’s immune system activity within 24 or 48 hours may be quite different.

The cross-talk between the peripheral nervous system and brain’s inherent immune system is dynamic. After routine surgery, a systemic surgical insult is associated with a subacute central immune suppression. This interaction between the peripheral and central immune system needs to be studied more extensively after brain injury.

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