Research Reports - Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome

J Neurosurg. 2012 Oct 12

Adamczak S, Dale G, de Rivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW

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.

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