Abstract 3549: Sex-Independent Down-regulation of MMP-9 with Minocycline after Experimental Embolic Stroke
Background and Purpose - Minocycline provides neurovascular protection reducing acute cerebral injury. However, it is unclear whether minocycline is effective in females. We tested minocycline in both sexes and aged animals using an embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans. The aim was to determine if there is a sex-specific change in MMP-9 levels.
Methods - In the context of the revised preclinical STAIR criteria call for testing of neuroprotective agents in female mice and aged mice, minocycline was tested in five groups of mice subjected to thromboembolic stroke: adult males, aged males, adult females, aged females, and adult ovariectomized females (n=9-23 animals/group). Behavioral outcomes, infarct volumes, and cerebral blood flow as well as expression and activity of MMP-9 were assessed. Statistical ANOVA analyses were performed using SAS® 9.2.
Results - The model resulted in reproducible infarct in the experimental groups. As expected, adult females were significantly more resistant to cerebral ischemic injury than males. This advantage was abolished by aging and ovariectomy. Minocycline significantly reduced the infarct volume (P=0.0001) and also improved neurologic score (P<0.0001) in all groups. Moreover, minocycline treatment significantly reduced mortality at 24 hours post stroke (P=0.037) for aged mice (25% versus 54%). Stroke up-regulated MMP-9 level in the brain and acute minocycline treatment reduced its expression in both genders (P<0.0001).
Conclusion - In a thromboembolic stroke model minocycline is neuroprotective inhibiting MMP-9 irrespective of mouse sex and age.
- © 2012 by American Heart Association, Inc.