title: Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke.
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).
  
  
  CONCLUSIONS
  In a thromboembolic stroke model minocycline is neuroprotective irrespective of mouse sex and age.
authors.affiliation: Department of Neurology, Georgia Health Sciences University, Augusta, GA, USA. isazonova@georgiahealth.edu.
authors.forename: Md Nasrul
authors.initials: MN
authors.lastname: Hoda
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Ajmal
authors.initials: A
authors.lastname: Ahmad
authors.forename: Safia
authors.initials: S
authors.lastname: Ogbi
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zemskova
authors.forename: Maribeth H
authors.initials: MH
authors.lastname: Johnson
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
authors.forename: David C
authors.initials: DC
authors.lastname: Hess
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Sazonova