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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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

Fingerprint

Matrix Metalloproteinase 8
Matrix Metalloproteinases
Matrix Metalloproteinase 2
Cerebrovascular Circulation
Matrix Metalloproteinase 7
Matrix Metalloproteinase 1
Intracranial Pressure
Neck
Matrix Metalloproteinase 3
Matrix Metalloproteinase 9
Microdialysis
Pyruvic Acid
Critical Illness
Brain Injuries
Cerebrospinal Fluid
Drainage
Lactic Acid
Catheters
Glucose
Mortality

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., ... 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

A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans. / Roberts, Derek J.; Jenne, Craig N.; Léger, Caroline; Kramer, Andreas H.; Gallagher, Clare N.; Todd, Stephanie; Parney, Ian F; Doig, Christopher J.; Yong, V. Wee; Kubes, Paul; Zygun, David A.

In: Journal of Neurotrauma, Vol. 30, No. 20, 15.10.2013, p. 1717-1726.

Research output: Contribution to journalArticle

Roberts, DJ, Jenne, CN, Léger, C, Kramer, AH, Gallagher, CN, Todd, S, Parney, IF, Doig, CJ, Yong, VW, Kubes, P & Zygun, DA 2013, 'A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans', Journal of Neurotrauma, vol. 30, no. 20, pp. 1717-1726. https://doi.org/10.1089/neu.2012.2841
Roberts, Derek J. ; Jenne, Craig N. ; Léger, Caroline ; Kramer, Andreas H. ; Gallagher, Clare N. ; Todd, Stephanie ; Parney, Ian F ; Doig, Christopher J. ; Yong, V. Wee ; Kubes, Paul ; Zygun, David A. / A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans. In: Journal of Neurotrauma. 2013 ; Vol. 30, No. 20. pp. 1717-1726.
@article{583341341b0347688a9b62a95790773a,
title = "A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans",
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.",
keywords = "brain injuries, cerebrospinal fluid, craniocerebral trauma, matrix metalloproteinase, microdialysis",
author = "Roberts, {Derek J.} and Jenne, {Craig N.} and Caroline L{\'e}ger and Kramer, {Andreas H.} and Gallagher, {Clare N.} and Stephanie Todd and Parney, {Ian F} and Doig, {Christopher J.} and Yong, {V. Wee} and Paul Kubes and Zygun, {David A.}",
year = "2013",
month = "10",
day = "15",
doi = "10.1089/neu.2012.2841",
language = "English (US)",
volume = "30",
pages = "1717--1726",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "20",

}

TY - JOUR

T1 - A prospective evaluation of the temporal matrix metalloproteinase response after severe traumatic brain injury in humans

AU - Roberts, Derek J.

AU - Jenne, Craig N.

AU - Léger, Caroline

AU - Kramer, Andreas H.

AU - Gallagher, Clare N.

AU - Todd, Stephanie

AU - Parney, Ian F

AU - Doig, Christopher J.

AU - Yong, V. Wee

AU - Kubes, Paul

AU - Zygun, David A.

PY - 2013/10/15

Y1 - 2013/10/15

N2 - 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.

AB - 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.

KW - brain injuries

KW - cerebrospinal fluid

KW - craniocerebral trauma

KW - matrix metalloproteinase

KW - microdialysis

UR - http://www.scopus.com/inward/record.url?scp=84885588793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885588793&partnerID=8YFLogxK

U2 - 10.1089/neu.2012.2841

DO - 10.1089/neu.2012.2841

M3 - Article

VL - 30

SP - 1717

EP - 1726

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 20

ER -