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  • BACKGROUND: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Recent trials in ICH, focusing on hematoma reduction, have not yielded significant clinical improvement. The modulation of matrix metalloproteinase (MMP)-9 may represent a potential therapeutic target for reducing perihematomal edema (PHE) and improving clinical outcome. METHODS: We searched Cochrane Library, Ovid/Medline, and PubMed databases using combinations of the following MeSH search terms: %22intracerebral hemorrhage,%22 %22matrix metalloproteinase,%22 %22minocycline,%22 %22inhibition,%22 and %22neuroprotection%22. RESULTS: MMP-9 levels in animal models have largely shown detrimental correlations with mortality, clinical outcome, hematoma volume, and PHE. Animal models and clinical studies have established a timeline for MMP-9 expression and corresponding PHE that include an initial peak on days 1-3 and a secondary peak on day 7. Clinical studies evaluating MMP-9 levels in the acute phase (days 1-3) and subacute phase (day 7) of ICH suggest that MMP-9 may be detrimental in the acute phase through destruction of basal lamina, activation of vascular endothelial growth factor, and activation of apoptosis but assist in recovery in the subacute phase through angiogenesis. CONCLUSIONS: MMP-9 inhibition represents a potentially effective target for neuroprotection in ICH. However, as a ubiquitous protein, the inhibition of pathologic processes must be balanced against the preservation of neuroprotective angiogenesis. As the opposing roles of MMP-9 may have similar mechanisms, the most important factor may be the timing of MMP-9 inhibition. Further studies are necessary to delineate these mechanisms and their temporal relationship.
  • BACKGROUND: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Recent trials in ICH, focusing on hematoma reduction, have not yielded significant clinical improvement. The modulation of matrix metalloproteinase (MMP)-9 may represent a potential therapeutic target for reducing perihematomal edema (PHE) and improving clinical outcome. METHODS: We searched Cochrane Library, Ovid/Medline, and PubMed databases using combinations of the following MeSH search terms: %22intracerebral hemorrhage,%22 %22matrix metalloproteinase,%22 %22minocycline,%22 %22inhibition,%22 and %22neuroprotection%22. RESULTS: MMP-9 levels in animal models have largely shown detrimental correlations with mortality, clinical outcome, hematoma volume, and PHE. Animal models and clinical studies have established a timeline for MMP-9 expression and corresponding PHE that include an initial peak on days 1-3 and a secondary peak on day 7. Clinical studies evaluating MMP-9 levels in the acute phase (days 1-3) and subacute phase (day 7) of ICH suggest that MMP-9 may be detrimental in the acute phase through destruction of basal lamina, activation of vascular endothelial growth factor, and activation of apoptosis but assist in recovery in the subacute phase through angiogenesis. CONCLUSIONS: MMP-9 inhibition represents a potentially effective target for neuroprotection in ICH. However, as a ubiquitous protein, the inhibition of pathologic processes must be balanced against the preservation of neuroprotective angiogenesis. As the opposing roles of MMP-9 may have similar mechanisms, the most important factor may be the timing of MMP-9 inhibition. Further studies are necessary to delineate these mechanisms and their temporal relationship. (en)
Title
  • Matrix Metalloproteinase-9: Dual Role and Temporal Profile in Intracerebral Hemorrhage
  • Matrix Metalloproteinase-9: Dual Role and Temporal Profile in Intracerebral Hemorrhage (en)
skos:prefLabel
  • Matrix Metalloproteinase-9: Dual Role and Temporal Profile in Intracerebral Hemorrhage
  • Matrix Metalloproteinase-9: Dual Role and Temporal Profile in Intracerebral Hemorrhage (en)
skos:notation
  • RIV/00159816:_____/14:00061227!RIV15-MSM-00159816
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED1.100/02/0123)
http://linked.open...iv/cisloPeriodika
  • 10
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
  • Tsivgoulis, Georgios
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 27681
http://linked.open...ai/riv/idVysledku
  • RIV/00159816:_____/14:00061227
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • perihematomal edema; neuroprotection; intracerebral hemorrhage; gelatinase B; blood brain barrier; Matrix metalloproteinase (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [65EEBC7E62EC]
http://linked.open...i/riv/nazevZdroje
  • Journal of Stroke & Cerebrovascular Diseases
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 23
http://linked.open...iv/tvurceVysledku
  • Tsivgoulis, Georgios
  • Alexandrov, A. V.
  • Chang, J. J.
  • Emanuel, B. A.
  • Mack, W. J.
http://linked.open...ain/vavai/riv/wos
  • 000345650300015
issn
  • 1052-3057
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.jstrokecerebrovasdis.2014.07.005
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