Matrix metalloproteinase-9

Dual role and temporal profile in intracerebral hemorrhage

Jason J. Chang, Benjamin A. Emanuel, William J. Mack, Georgios Tsivgoulis, Andrei Alexandrov

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

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: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". 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

Original languageEnglish (US)
Pages (from-to)2498-2505
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number10
DOIs
StatePublished - Jan 1 2014

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Matrix Metalloproteinase 9
Cerebral Hemorrhage
Edema
Hematoma
Animal Models
Minocycline
Pathologic Processes
Matrix Metalloproteinases
Basement Membrane
PubMed
Vascular Endothelial Growth Factor A
Libraries
Databases
Apoptosis
Mortality

All Science Journal Classification (ASJC) codes

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Matrix metalloproteinase-9 : Dual role and temporal profile in intracerebral hemorrhage. / Chang, Jason J.; Emanuel, Benjamin A.; Mack, William J.; Tsivgoulis, Georgios; Alexandrov, Andrei.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 10, 01.01.2014, p. 2498-2505.

Research output: Contribution to journalReview article

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abstract = "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: {"}intracerebral hemorrhage,{"} {"}matrix metalloproteinase,{"} {"}minocycline,{"} {"}inhibition,{"} and {"}neuroprotection{"}. 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",
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N2 - 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: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". 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

AB - 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: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". 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

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