Matrix Metalloproteinase Regulation in Intracerebral Hemorrhage

Jason J Chang, G. Morgan Jones, Anna Betlachin, Tayebeh Pourmotabbed


Intracerebral hemorrhage remains a particularly devastating form of cerebrovascular disease with unchanged mortality rates despite several large studies that have targeted primary expansion of hematoma growth. A second, worthwhile target for improving clinical outcome after intracerebral hemorrhage may be neuroprotection through modulation of secondary mechanisms of brain injury. Matrix metalloproteinases represent a family of ubiquitous endopeptidase enzymes that can become pathologically activated and result in blood-brain barrier breakdown. In humans, high levels of matrix metalloproteinase have been associated with perihematomal edema, symptomatic hemorrhagic transformation, and worse clinical outcome. As a result, inhibition of matrix metalloproteinase in the acute phase of intracerebral hemorrhage may represent an efficacious strategy for improving clinical outcome. Current strategies for inhibiting matrix metalloproteinase in intracerebral hemorrhage are as follows: (1) direct inhibition, (2) transcriptional control of matrix metalloproteinase expression, and (3) post-transcriptional control. Currently, the most clinically relevant form of matrix metalloproteinase inhibition lies with direct inhibition through broad-spectrum hydroxamate-class inhibitors and tetracycline-class antibiotics and the polymechanistic role of statins. Further trials are necessary to evaluate for possible roles of matrix metalloproteinase inhibition in improving clinical outcome after intracerebral hemorrhage.


Cerebrovascular disease; Intracerebral hemorrhage; Inhibition; Matrix metalloproteinase; Neuroprotection

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