{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T06:59:35Z","timestamp":1785653975075,"version":"3.56.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:p> Elevated plasma homocysteine (Hcy) is associated with cerebrovascular disease and activates matrix metalloproteinases (MMPs), which lead to vascular remodeling that could disrupt the blood-brain barrier. To determine whether Hcy administration can increase brain microvascular leakage secondary to activation of MMPs, we examined pial venules by intravital video microscopy through a craniotomy in anesthetized mice. Bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) was injected into a carotid artery to measure extravenular leakage. Hcy (30 \u03bcM\/total blood volume) was injected 10 min after FITC-BSA injection. Four groups of mice were examined: 1) wild type (WT) given vehicle; 2) WT given Hcy (WT + Hcy); 3) MMP-9 gene knockout given Hcy (MMP-9\u2212\/\u2212 + Hcy); and 4) MMP-9\u2212\/\u2212 with topical application of histamine (10<jats:sup>\u22124<\/jats:sup> M) (MMP-9\u2212\/\u2212 + histamine). In the WT + Hcy mice, leakage of FITC-BSA from pial venules was significantly ( P &lt; 0.05) greater than in the other groups. There was no significant leakage of pial microvessels in MMP-9\u2212\/\u2212 + Hcy mice. Increased cerebrovascular leakage in the MMP-9\u2212\/\u2212 + histamine group showed that microvascular permeability could still increase by a mechanism independent of MMP-9. Treatment of cultured mouse microvascular endothelial cells with 30 \u03bcM Hcy resulted in significantly greater F-actin formation than in control cells without Hcy. Treatment with a broad-range MMP inhibitor (GM-6001; 1 \u03bcM) ameliorated Hcy-induced F-actin formation. 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