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Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children

Wallisch, Jessica S. and Simon, Dennis W. and Bayır, Hülya and Bell, Michael J. and Kochanek, Patrick M. and Clark, Robert S. B. (2017) Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children. Neurocritical Care, 27 (1). pp. 44-50. ISSN 1541-6933

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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] ≤8) 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 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 <24 h post-TBI. CSF NLRP3 levels were increased in TBI patients compared with controls at all time points, p < 0.001. TBI patients ≤4 years of age had higher peak NLRP3 levels versus patients >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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Wallisch, Jessica S.
Simon, Dennis
Bayır, Hülya
Bell, Michael J.
Kochanek, Patrick M.
Clark, Robert S. B.
Date: 2017
Date Type: Publication
Journal or Publication Title: Neurocritical Care
Volume: 27
Number: 1
Publisher: Springer
Page Range: pp. 44-50
DOI or Unique Handle: 10.1007/s12028-017-0378-7
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: No
ISSN: 1541-6933
Official URL:
Article Type: Research Article
Date Deposited: 08 Jun 2020 13:12
Last Modified: 08 Jun 2020 13:12


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