Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study
Journal of Neurotrauma
Mary Ann Liebert
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Guilfoyle, M., Carpenter, K., Helmy, A., Pickard, J., Menon, D., & Hutchinson, P. (2015). Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study. Journal of Neurotrauma, 32 1553-1559. https://doi.org/10.1089/neu.2014.3764
Matrix metalloproteinases (MMPs) are extracellular enzymes that have been implicated in the pathophysiology of blood– brain barrier (BBB) breakdown, contusion expansion, and vasogenic edema after traumatic brain injury (TBI). Specifically, in focal injury models, increased MMP-9 expression has been observed in pericontusional brain, and MMP-9 inhibitors reduce brain swelling and final lesion volume. The aim of this study was to examine whether there is a similarly localized increase of MMP concentrations in patients with contusional TBI. Paired microdialysis catheters were inserted into 12 patients with contusional TBI (with or without associated mass lesion) targeting pericontusional and radiologically normal brain defined on admission computed tomography scan. Microdialysate was pooled every 8 h and analyzed for MMP-1, -2, -7, -9, and -10 using a multiplex immunoassay. Concentrations of MMP-1, -2, and -10 were similar at both monitoring sites and did not show discernible temporal trends. Overall, there was a gradual increase in MMP-7 concentrations in both normal and injured brain over the monitoring period, although this was not consistent in every patient. MMP-9 concentrations were elevated in pericontusional, compared to normal, brain, with the maximal difference at the earliest monitoring times (i.e., < 24 h postinjury). Repeated-measures analysis of variance showed that MMP-9 concentrations were significantly higher in pericontusional brain ( p = 0.03) and within the first 72 h of injury, compared with later in the monitoring period ( p = 0.04). No significant differences were found for the other MMPs assayed. MMP-9 concentrations are increased in pericontusional brain early post-TBI and may represent a potential therapeutic target to reduce hemorrhagic progression and vasogenic edema.
adult brain injury, extracellular matrix, microdialysis
M.R.G. was supported by a National Institute for Health Research (NIHR) Academic Clinical Fellowship, a Royal College of Surgeons/Philip King Research Fellowship, and a Beverley and Raymond Sackler Fellowship. A.H. was supported by a joint Medical Research Council/ Royal College of Surgeons of England Clinical Research Training Fellowship. K.L.H.C. is supported by the NIHR Biomedical Research Center, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). J.D.P. is supported by the Traumatic Brain Injury NIHR Health Technology Cooperative. D.K.M. is supported by an NIHR Senior Investigator Award. P.J.A.H. is supported by the Cambridge NIHR BRC and an NIHR Research Professorship.
External DOI: https://doi.org/10.1089/neu.2014.3764
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248055
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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