Journal ArticleDOI
Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.
Raj G. Kumar,Matthew L. Diamond,Jennifer A. Boles,Rachel P. Berger,S.A. Tisherman,Patrick M. Kochanek,Amy K. Wagner +6 more
TLDR
Evidence is provided that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases areassociated with increased odds for unfavorable global outcomes in the first year following TBI.Abstract:
Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.read more
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Journal ArticleDOI
The far-reaching scope of neuroinflammation after traumatic brain injury
Dennis W. Simon,Mandy J. McGeachy,Hülya Bayır,Robert S. B. Clark,David J. Loane,Patrick M. Kochanek +5 more
TL;DR: A new framework of targeted immunomodulation after TBI is proposed that incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options and highlights findings that could offer novel therapeutic targets for translational and clinical research.
Journal ArticleDOI
Traumatic brain injuries.
Kaj Blennow,David L. Brody,Patrick M. Kochanek,Harvey S. Levin,Ann C. McKee,Gerard M. Ribbers,Kristine Yaffe,Henrik Zetterberg,Henrik Zetterberg,Henrik Zetterberg +9 more
TL;DR: MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE.
Journal ArticleDOI
Fluid biomarkers for mild traumatic brain injury and related conditions
Henrik Zetterberg,Kaj Blennow +1 more
TL;DR: The literature on fluid biomarkers for neuronal, axonal, oligodendrocytic, astroglial and blood–brain barrier injury, as well as markers for neuroinflammation and metabolic dysregulation, in the context of mild TBI, PCS and CTE are reviewed.
Journal ArticleDOI
Emerging Roles for the Immune System in Traumatic Brain Injury.
Celia A. McKee,John R. Lukens +1 more
TL;DR: This review will cover insights gained from studies that approach TBI research from an immunological perspective and will summarize the current understanding of the involvement of specific immune cell types and cytokines in TBI pathogenesis.
Journal ArticleDOI
Priming the inflammatory pump of the CNS after traumatic brain injury.
TL;DR: The evidence that microglia become primed following TBI is discussed and how this corresponds with vulnerability to a 'second hit' and subsequent neuropsychiatric and neurodegenerative complications is discussed.
References
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The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care
TL;DR: Results of this investigation indicate that the Injury Severity Score represents an important step in solving the problem of summarizing injury severity, especially in patients with multiple trauma.
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Regression Models for Categorical and Limited Dependent Variables
TL;DR: In this article, the authors propose Continuous Outcomes Binary Outcomes Testing and Fit Ordinal Outcomes Numeric Outcomes and Numeric Numeric Count Outcomes (NOCO).
Journal ArticleDOI
ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE: A Practical Scale
Bryan Jennett,Michael R. Bond +1 more
TL;DR: In this article, a five-point scale is described, which includes death, persistent vegetative state, severe disability, moderate disability, and good recovery, and duration as well as intensity of disability should be included in an index of ill-health.
Journal ArticleDOI
Regression Models for Categorical and Limited Dependent Variables
TL;DR: Introduction Continuous Outcomes Binary Outcomes Testing and Fit Ordinal Outcomes Nominal outcomes Limited Outcomes Count Outcomes Conclusions