Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome
Clinical article
Search for other papers by Stephanie Adamczak in
Current site
Google Scholar
PubMed
Search for other papers by Gordon Dale in
Current site
Google Scholar
PubMed
Search for other papers by Juan Pablo de Rivero Vaccari in
Current site
Google Scholar
PubMed
Search for other papers by M. Ross Bullock in
Current site
Google Scholar
PubMed
Search for other papers by W. Dalton Dietrich in
Current site
Google Scholar
PubMed
Search for other papers by Robert W. Keane in
Current site
Google Scholar
PubMed
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.
Abbreviations used in this paper:
ASC = apoptosis-associated speck-like protein containing a caspase recruitment domain; ATV = all-terrain vehicle; DAMP = damage-associated molecular pattern; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; IL = interleukin; MVA = motor vehicle accident; NALP-1 = Nacht leucine-rich-repeat protein–1; TBI = traumatic brain injury.
© Copyright 1944-2024 American Association of Neurological Surgeons. All rights reserved, including those for text and data mining, AI training, and similar technologies.