White Matter Damage and the Effect of Matrix Metalloproteinases in Type 2 Diabetic Mice After Stroke

Diabetes mellitus leads to a higher risk of ischemic stroke and worse outcome compared to the general population. However, there have been few studies on white matter (WM) damage after stroke in diabetes mellitus. We therefore investigated WM damage after stroke in mice with diabetes mellitus. BKS.Cg-m(+/+)Lepr(db)/J (db/db) type 2 diabetes mellitus mice and db(+) non-diabetes mellitus mice were subjected to middle cerebral artery occlusion. Functional outcome, immunostaining, zymography, Western blot, and polymerase chain reaction were used. After stroke, mice with diabetes mellitus exhibited significantly increased lesion volume and brain hemorrhagic and neurological deficits compared to mice without diabetes mellitus. Bielshowsky silver, luxol fast blue, amyloid precursor protein, and NG2 expression were significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)-9 activity was significantly increased in the ischemic brain of mice with diabetes mellitus. Subanalysis of similar lesions in mice with and without diabetes mellitus demonstrated mice with diabetes mellitus had significantly increased WM damage than in mice without diabetes mellitus (P