Association between the cerebral inflammatory and matrix metalloproteinase responses after severe traumatic brain injury in humans

Derek J. Roberts, Craig N. Jenne, Caroline Léger, Andreas H. Kramer, Clare N. Gallagher, Stephanie Todd, Ian F. Parney, Christopher J. Doig, V. Wee Yong, Paul Kubes, David A. Zygun

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

An increasing number of preclinical investigations have suggested that the degree of expression of the matrix metalloproteinase (MMP) family of endopeptidases may explain some of the variability in neurological damage after traumatic brain injury (TBI). As cytokines are a prominent stimulus for MMP expression in animals, we conducted a prospective multimodal monitoring study and determined their association with temporal MMP expression after severe TBI in eight critically ill adults. High cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to measure the concentration of nine cytokines and eight MMPs in microdialysate, cerebrospinal fluid (CSF), and plasma over 6 days. Severe TBI was associated with a robust central inflammatory response, which was largely similar between microdialysate and CSF. At all time points after injury, this response was predominated by the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. Use of univariate generalized estimating equations suggested that the concentration of several MMPs varied with cytokine levels in microdialysate. The largest of these changes included increases in microdialysate concentrations of MMP-8 and MMP-9 with increases in the levels of IL-1α and -2 and IL-1α and -2 and TNF-α, respectively. In contrast, the microdialysate level of MMP-7 decreased with increases in microdialysate concentrations of IL-1β, -2, and -6. These findings support the observations of animal studies that cross-talk exists between the neuroinflammatory and MMP responses after acute brain injury. Further study is needed to determine whether this link between cerebral inflammation and MMP expression may have clinical relevance to the care of patients with TBI.

Original languageEnglish (US)
Pages (from-to)1727-1736
Number of pages10
JournalJournal of neurotrauma
Volume30
Issue number20
DOIs
StatePublished - Oct 15 2013

Keywords

  • brain injuries
  • cerebrospinal fluid
  • craniocerebral trauma
  • cytokines
  • matrix metalloproteinases
  • microdialysis
  • neuroinflammation

ASJC Scopus subject areas

  • Clinical Neurology

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    Roberts, D. J., Jenne, C. N., Léger, C., Kramer, A. H., Gallagher, C. N., Todd, S., Parney, I. F., Doig, C. J., Yong, V. W., Kubes, P., & Zygun, D. A. (2013). Association between the cerebral inflammatory and matrix metalloproteinase responses after severe traumatic brain injury in humans. Journal of neurotrauma, 30(20), 1727-1736. https://doi.org/10.1089/neu.2012.2842