Warfarin Pretreatment Reduces Cell Death and MMP-9 Activity in Experimental Intracerebral Hemorrhage

There is a slight problem here in that you would need to know you're going to have a hemorrhage so you can pretreat yourself. Or maybe you'd rather go to high altitudes for Training the Brain to Survive Stroke.
http://link.springer.com/article/10.1007/s12975-014-0377-3

• Frieder Schlunk,
• Elena Schulz,
• Arne Lauer,
• Kazim Yigitkanli,
• Waltraud Pfeilschifter,
• Helmuth Steinmetz,
• Eng H. Lo,
• Christian Foerch

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Abstract

Little is known about the pathophysiology of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH). We compared hematoma volume, number of terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL)-positive cells (indicating cell death), MMP-9 levels, and perilesional edema formation between warfarin-treated mice and controls. Intracerebral hemorrhage was induced by an injection of collagenase into the right striatum. Twenty-four hours later, hematoma volume was measured using a photometric hemoglobin assay. Cell death was quantified using TUNEL staining. MMP-9 levels were determined by zymography, and edema formation was assessed via the wet–dry method. Warfarin increased hematoma volume by 2.6-fold. The absolute number of TUNEL-positive cells in the perihematomal zone was lower in warfarin-treated animals (300.5 ± 39.8 cells/mm²) than in controls (430.5 ± 38.9 cells/mm²; p = 0.034), despite the larger bleeding volume. MMP-9 levels were reduced in anticoagulated mice as compared to controls (p  = 0.018). Perilesional edema formation was absent in warfarin mice and modestly present in controls. Our results suggest differences in the pathophysiology of OAC-ICH compared to intracerebral hemorrhage occurring under normal coagulation. A likely explanation is that thrombin, a strong inductor of apoptotic cell death and blood–brain barrier disruption, is produced to a lesser extent in OAC-ICH. In humans, however, we assume that the detrimental effects of a larger hematoma volume in OAC-ICH by far outweigh potential protective effects of thrombin deficiency.