Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children
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ORIGINAL ARTICLE
Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children Jessica S. Wallisch1,2,3 • Dennis W. Simon1,2,3 • Hu¨lya Bayır1,2,3,4 • Michael J. Bell1,2,3,5 • Patrick M. Kochanek1,2,3 • Robert S. B. Clark1,2,3
Ó Springer Science+Business Media New York 2017
Abstract Background Inflammasome-mediated neuroinflammation may cause secondary injury following traumatic brain injury (TBI) in children. The pattern recognition receptors NACHT domain-, Leucine-rich repeat-, and PYD-containing Protein 1 (NLRP1) and NLRP3 are essential components of their respective inflammasome complexes. We sought to investigate whether NLRP1 and/or NLRP3 abundance is altered in children with severe TBI. Methods Cerebrospinal fluid (CSF) from children (n = 34) with severe TBI (Glasgow coma scale score [GCS] B8) who had externalized ventricular drains (EVD) placed for routine care was evaluated for NLRP1 and NLRP3 at 0–24, 25–48, 49–72, and >72 h post-TBI and was compared to infection-free controls that underwent
Jessica S. Wallisch and Dennis W. Simon have contributed equally to this work. & Dennis W. Simon [email protected] 1
Department of Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
2
Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3
Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
5
Department of Neurological Surgery, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
lumbar puncture to rule out CNS infection (n = 8). Patient age, sex, initial GCS, mechanism of injury, treatment with therapeutic hypothermia, and 6-month Glasgow outcome score were collected. Results CSF NLRP1 was undetectable in controls and detected in 2 TBI patients at only 4 (15.50 [3.65–25.71] vs. 3.04 [1.52–8.87] ng/ mL, respectively; p = 0.048). Controlling for initial GCS in multivariate analysis, peak NLRP3 >6.63 ng/mL was independently associated with poor outcome at 6 months. Conclusions In the first report of NLRP1 and NLRP3 in childhood neurotrauma, we found that CSF NLRP3 is elevated in children with severe TBI and independently associated with younger age and poor outcome. Future studies correlating NLRP3 with other markers of inflammation and response to therapy are warranted. Keywords NLRP3 NLRP1 Inflammasome Traumatic brain injury Biomarker Neuroinflammation Secondary brain injury Pediatric
Introduction Traumatic brain injury (TBI) accounts for over 60,000 hospitalizations in children per year in the USA alone and is a major cause of trauma-related morbidity and mortality [1, 2]. The neuroinflammatory
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