Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke
AuthorsHoda, Md Nasrul
Zemskova, Marina A
Johnson, Maribeth H.
Hill, William D
Hess, David C.
Sazonova, Irina Y
MetadataShow full item record
AbstractBackground: 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.
CitationExp Transl Stroke Med. 2011 Dec 16; 3:16
- A 2 × 2 factorial design for the combination therapy of minocycline and remote ischemic perconditioning: efficacy in a preclinical trial in murine thromboembolic stroke model.
- Authors: Hoda MN, Fagan SC, Khan MB, Vaibhav K, Chaudhary A, Wang P, Dhandapani KM, Waller JL, Hess DC
- Issue date: 2014
- Sex-dependent effects of G protein-coupled estrogen receptor activity on outcome after ischemic stroke.
- Authors: Broughton BR, Brait VH, Kim HA, Lee S, Chu HX, Gardiner-Mann CV, Guida E, Evans MA, Miller AA, Arumugam TV, Drummond GR, Sobey CG
- Issue date: 2014 Mar
- Minocycline and tissue-type plasminogen activator for stroke: assessment of interaction potential.
- Authors: Machado LS, Sazonova IY, Kozak A, Wiley DC, El-Remessy AB, Ergul A, Hess DC, Waller JL, Fagan SC
- Issue date: 2009 Sep
- Sex differences in minocycline-induced neuroprotection after experimental stroke.
- Authors: Li J, McCullough LD
- Issue date: 2009 Apr
- Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke.
- Authors: Machado LS, Kozak A, Ergul A, Hess DC, Borlongan CV, Fagan SC
- Issue date: 2006 Jul 17