Tissue Protease Suppression of Value in Brain Hemorrhage

Animal study suggests therapeutic potential of inhibiting matrix metalloproteinase-9

THURSDAY, Oct. 4 (HealthDay News) -- Suppression of matrix metalloproteinase-9 may attenuate vascular endothelial growth-factor induced intracerebral hemorrhage, suggesting that matrix metalloproteinase-9 inhibitors may be of use in treating cerebral vascular rupture, according to the results of an animal study published in the September issue of Stroke.

William L. Young, M.D., of the University of California San Francisco, and colleagues used a mouse model to test the effects of minocycline, a non-specific matrix metalloproteinase inhibitor, and pyrrolidine dithiocarbamate, an upstream regulator of matrix metalloproteinases, on matrix metalloproteinase-9 activity and the degree of intracerebral hemorrhage.

The researchers found that both drugs suppressed vascular endothelial growth factor-induced matrix metalloproteinase-9 activity and the associated increases in hemoglobin levels.

"The mechanism of matrix metalloproteinase inhibition by tetracyclines has not been fully understood," the authors write. "Additionally, the causal relationship between matrix metalloproteinase-9 activity and hemorrhage needs to be more precisely defined in future studies. We did note a trend toward a positive correlation between the matrix metalloproteinase-9 levels and extent of bleeding in the brain tissue. It is also critical that further studies use more specific inhibitors that target only individual matrix metalloproteinases, e.g., matrix metalloproteinase-9, or matrix metalloproteinase-9 knockout mice. These studies would help define the mechanisms underlying the pathogenesis of vascular endothelial growth-factor induced intracerebral hemorrhage and thus provide more specific therapeutic targets."

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