Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: Clinical article

Stephanie Adamczak, Gordon Dale, Juan Pablo De Rivero Vaccari, M. Ross Bullock, W. Dalton Dietrich, Robert W. Keane

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Object. Traumatic brain injury (TBI), the third most common CNS pathology, plagues 5.3 million Americans with permanent TBI-related disabilities. To evaluate injury severity and prognosis, physicians rely on clinical variables. Here, the authors seek objective, biochemical markers reflecting molecular injury mechanisms specific to the CNS as more accurate measurements of injury severity and outcome. One such secondary injury mechanism, the innate immune response, is regulated by the inflammasome, a molecular platform that activates caspase-1 and interleukin-1β. Methods. The authors investigated whether inflammasome components were present in the CSF of 23 patients with TBI and whether levels of inflammasome components correlate with outcome. The authors performed an immunoblot analysis of CSF samples from patients who suffered TBI and nontrauma controls and assessed the outcomes 5 months postinjury by using the Glasgow Outcome Scale. Data were analyzed using Mann-Whitney U-tests and linear regression analysis. Results. Patients with severe or moderate cranial trauma exhibited significantly higher CSF levels of the inflammasome proteins ASC, caspase-1, and NALP-1 than nontrauma controls (p < 0.0001, p = 0.0029, and p = 0.0202, respectively). Expression of each protein correlated significantly with the Glasgow Outcome Scale score at 5 months postinjury (p < 0.05). ASC, caspase-1, and NALP-1 were significantly higher in the CSF of patients with unfavorable outcomes, including death and severe disability (p < 0.0001). Conclusions. NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors.

Original languageEnglish (US)
Pages (from-to)1119-1125
Number of pages7
JournalJournal of neurosurgery
Volume117
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Biomarker
  • Inflammasome
  • Inflammation
  • Innate immunity
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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