Document Detail


Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article.
MedLine Citation:
PMID:  23061392     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Stephanie Adamczak; Gordon Dale; Juan Pablo de Rivero Vaccari; M Ross Bullock; W Dalton Dietrich; Robert W Keane
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-12
Journal Detail:
Title:  Journal of neurosurgery     Volume:  117     ISSN:  1933-0693     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-01-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1119-25     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Florida, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / cerebrospinal fluid*
Adolescent
Adult
Aged
Apoptosis Regulatory Proteins / cerebrospinal fluid*
Biological Markers / cerebrospinal fluid
Brain Injuries / cerebrospinal fluid*,  immunology*,  pathology,  physiopathology
Case-Control Studies
Caspase 1 / cerebrospinal fluid*
Cytoskeletal Proteins / cerebrospinal fluid*
Female
Glasgow Coma Scale
Glasgow Outcome Scale
Humans
Immunity, Innate*
Inflammasomes / cerebrospinal fluid*
Injury Severity Score
Male
Middle Aged
Predictive Value of Tests
Prognosis
Recovery of Function
Grant Support
ID/Acronym/Agency:
NS032091/NS/NINDS NIH HHS; P50 NS030291/NS/NINDS NIH HHS; R01 NS042133/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/Biological Markers; 0/Cytoskeletal Proteins; 0/Inflammasomes; 0/NLRP1 protein, human; 0/PYCARD protein, human; EC 3.4.22.36/Caspase 1
Comments/Corrections

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