A prospective evaluation of the temporal matrix metalloproteinase response 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

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Abstract

Accumulating pre-clinical data suggests that matrix metalloproteinase (MMP) expression plays a critical role in the pathophysiology of secondary brain injury. We conducted a prospective multimodal monitoring study in order to characterize the temporal MMP response after severe traumatic brain injury (TBI) in eight critically ill humans and its relationship with outcomes. High-cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to collect microdialysate, cerebrospinal fluid, and arterial and jugular bulb blood over 6 days. Levels of MMP-8 and -9 were initially high in microdialysate and then gradually declined over time. After these MMPs decreased, a spike in the microdialysate levels of MMP-2 and -3 occurred, followed by a gradual rise in the microdialysate concentration of MMP-7. Use of generalized estimating equations suggested that MMP-8 concentration in microdialysate was associated with mortality (p=0.019) and neurological outcome at hospital discharge (p=0.013). Moreover, the mean microdialysate concentration of MMP-8 was 2.4-fold higher among those who died after severe TBI than in those who survived. Mean microdialysate levels of MMP-8 also rose with increasing intracranial pressure (ICP), whereas those of MMP-7 decreased with increasing cerebral perfusion pressure (CPP). Significant changes in the mean microdialysate concentrations of MMP-1, -2, -3, and -9 and MMP-1, -2, -3, -7, and -9 also occurred with increases in microdialysate glucose and the lactate/pyruvate ratio, respectively. These results imply that monitoring of MMPs following severe TBI in humans is feasible, and that their expression may be associated with clinical outcomes, ICP, CPP, and cerebral metabolism.

Original languageEnglish (US)
Pages (from-to)1717-1726
Number of pages10
JournalJournal of neurotrauma
Volume30
Issue number20
DOIs
StatePublished - Oct 15 2013

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Keywords

  • brain injuries
  • cerebrospinal fluid
  • craniocerebral trauma
  • matrix metalloproteinase
  • microdialysis

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

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). A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans. Journal of neurotrauma, 30(20), 1717-1726. https://doi.org/10.1089/neu.2012.2841