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Brain Behav Immun. 2015 Mar;45:15-27. doi: 10.1016/j.bbi.2014.09.003. Epub 2014 Sep 16.

Variable neuroendocrine-immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury.

Author information

1
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, USA. Electronic address: martina.santarsieri@gmail.com.
2
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, USA. Electronic address: kumarr4@upmc.edu.
3
Safar Center for Resuscitation Research, University of Pittsburgh, USA; Department of Critical Care Medicine, University of Pittsburgh, USA. Electronic address: kochanekpm@ccm.upmc.edu.
4
Department of Obstetrics and Gynecology, Wake Forest University, USA. Electronic address: sberga@wakehealth.edu.
5
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, USA; Center for Neuroscience, University of Pittsburgh, USA; Safar Center for Resuscitation Research, University of Pittsburgh, USA. Electronic address: wagnerak@upmc.edu.

Abstract

Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate=-0.253, 95% CI (-0.481, -0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=-0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune dysfunction differs between cortisol TRAJ groups. These results present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.

KEYWORDS:

Cell adhesion molecule; Cerebrospinal fluid; Cortisol; Cytokines; GOS; Hypothalamic–pituitary-axis; Inflammation; Rehabilomics; Trajectory analysis; Traumatic brain injury

PMID:
25218898
PMCID:
PMC4342288
DOI:
10.1016/j.bbi.2014.09.003
[Indexed for MEDLINE]
Free PMC Article

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