Model System:

TBI

Reference Type:

Journal

Accession No.:

J73539

Journal:


Brain, Behavior, and Immunity

Year, Volume, Issue, Page(s):

, 45, , 15-27

Publication Website:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342288/

Abstract:

Study examined relationships between cerebrospinal fluid (CSF) cortisol and inflammation after traumatic brain injury (TBI) and determined how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI, analyzed for cortisol and inflammatory markers, and compared to healthy controls (13 controls were analyzed for cortisol, 11 for inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high versus low cortisol). Glasgow Outcome Scale (GOS) scores at 6 months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome. 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. Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol. The 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 findings present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.

Author(s):


Santarsieri, Martina, Kumar, Raj G., Kochanek, Patrick M., Berga, Sarah L., Wagner, Amy K.

Participating Centers: