Homocysteine causes cerebrovascular leakage in mice

vated 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 micros-copy 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 M/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/ Hcy); and 4) MMP-9/ with topical application of histamine (104 M) (MMP-9/ histamine). In the WT Hcy mice, leakage of FITC-BSA from pial venules was significantly (P 0.05) greater than in the other groups. There was no significant leakage of pial microvessels in MMP-9/Hc