Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article.
OBJECTIVE
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.
Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Florida, USA.
Stephanie
S
Adamczak
Gordon
G
Dale
Juan Pablo
JP
de Rivero Vaccari
M Ross
MR
Bullock
W Dalton
WD
Dietrich
Robert W
RW
Keane
D048868:Adaptor Proteins, Signal Transducing / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D053468:CARD Signaling Adaptor Proteins; D016022:Case-Control Studies; D020170:Caspase 1 / Q000134:cerebrospinal fluid*; D003598:Cytoskeletal Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000134:cerebrospinal fluid*; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D000070576:NLR Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D020127:Recovery of Function
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C402202:PYCARD protein, human; D020170:Caspase 1