Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke

MD Nasrul Hoda, Weiguo Li, Ajmal Ahmad, Safia Ogbi, Marina A. Zemskova, Maribeth H Johnson, Adviye Ergul, William D Hill, David C Hess, Irina Yurievna Sazonova

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Article number16
JournalExperimental and Translational Stroke Medicine
Volume3
Issue number1
DOIs
StatePublished - Dec 16 2011

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Minocycline
Stroke
Matrix Metalloproteinases
Cerebrovascular Circulation
Neuroprotection
Wounds and Injuries
Ovariectomy
Nervous System
Phosphates
Mortality

Keywords

  • Animal model
  • MMP-9
  • Minocycline
  • Neuroprotection
  • Sex
  • Thromboembolic stroke

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cognitive Neuroscience

Cite this

Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. / 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 Yurievna.

In: Experimental and Translational Stroke Medicine, Vol. 3, No. 1, 16, 16.12.2011.

Research output: Contribution to journalArticle

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 Yurievna. / Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. In: Experimental and Translational Stroke Medicine. 2011 ; Vol. 3, No. 1.
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AB - 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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