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Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke

Author(s): Hoda Md Nasrul | Li Weiguo | Ahmad Ajmal | Ogbi Safia | Zemskova Marina A | Johnson Maribeth H | Ergul Adviye | Hill William D | Hess David C | Sazonova Irina Y

Journal: Experimental & Translational Stroke Medicine
ISSN 2040-7378

Volume: 3;
Issue: 1;
Start page: 16;
Date: 2011;
Original page

Keywords: thromboembolic stroke | animal model | neuroprotection | minocycline | sex | MMP-9

Abstract Background 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 a novel embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans. Methods Five groups of mice were subjected to thromboembolic stroke: adult males, aged males, adult females, aged females, and adult ovariectomized females. They were treated with phosphate saline (vehicle) or minocycline (6 mg/kg) immediately after stroke onset. Behavioral outcomes, infarct volumes and cerebral blood flow were assessed. The effect of minocycline on expression and activity of MMP-9 was analyzed. 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 irrespective of mouse sex and age.

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