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Minocycline down‐regulated MMP‐9 and PARP in male and female mice in an embolic model of ischemic stroke
Author(s) -
Sazonova Irina Y,
Hoda Md Nasrul,
Zemskova Marina A,
Hess David C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.662.13
Subject(s) - minocycline , neuroprotection , medicine , stroke (engine) , ovariectomized rat , anesthesia , cardiology , estrogen , biology , antibiotics , mechanical engineering , microbiology and biotechnology , engineering
Background and Purpose Acute ischemic stroke is one of the leading causes of morbidity and mortality in the U.S. Recently, minocycline has been shown to provide neurovascular protection reducing acute cerebral injury by means of its efficiency to inhibit MMP‐9 and PARP. However, it is unclear whether minocycline is effective in females. Here, our aim was to determine if there is a sex‐specific change in MMP‐9 and PARP levels in response to minocycline treatment. We analyzed the neuroprotective mechanisms of minocycline in both sexes using an embolic stroke model in mice that closely mimics acute thromboembolic stroke in humans. Methods Embolic stroke was initiated by injection of a thrombus to the right middle cerebral artery. Minocycline was tested in adult males and adult ovariectomized females (23±3 weeks old; n=9–23 animals/group). Behavioral outcomes, infarct volumes, and expression of MMP‐9, PARP, and caspase‐3 were assessed. Results Without minocycline treatment, cerebral blood flow, infarct size, and neurological scores were comparable in both males and ovariectomized females. Stroke up‐regulated MMP‐9 and PARP levels in the brain in both genders, and caspase‐3 level in females. Minocycline significantly reduced the infarct volume (P<0.0001), improved neurologic score (P<0.0001) and reduced expression of MMP‐9 (p<0.05) and PARP (p<0.05) in all animals. However, minocycline did not affect caspase‐3 levels. Conclusion In a thromboembolic stroke model minocycline is neuroprotective inhibiting MMP‐9 and PARP irrespective of mouse sex. Research support: NIH‐R21 award and GHSU start‐up to I.Y.S