Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke

Hdl Handle:
http://hdl.handle.net/10675.2/780
Title:
Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke
Authors:
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
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.
Citation:
Exp Transl Stroke Med. 2011 Dec 16; 3:16
Issue Date:
16-Dec-2011
URI:
http://hdl.handle.net/10675.2/780
DOI:
10.1186/2040-7378-3-16
PubMed ID:
22177314
PubMed Central ID:
PMC3287111
Type:
Article
ISSN:
2040-7378
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorHoda, Md Nasrulen_US
dc.contributor.authorLi, Weiguoen_US
dc.contributor.authorAhmad, Ajmalen_US
dc.contributor.authorOgbi, Safiaen_US
dc.contributor.authorZemskova, Marina Aen_US
dc.contributor.authorJohnson, Maribeth H.en_US
dc.contributor.authorErgul, Adviyeen_US
dc.contributor.authorHill, William Den_US
dc.contributor.authorHess, David C.en_US
dc.contributor.authorSazonova, Irina Yen_US
dc.date.accessioned2012-10-26T20:30:43Z-
dc.date.available2012-10-26T20:30:43Z-
dc.date.issued2011-12-16en_US
dc.identifier.citationExp Transl Stroke Med. 2011 Dec 16; 3:16en_US
dc.identifier.issn2040-7378en_US
dc.identifier.pmid22177314en_US
dc.identifier.doi10.1186/2040-7378-3-16en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/780-
dc.description.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.en_US
dc.description.abstractMethods: 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.en_US
dc.description.abstractResults: 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).en_US
dc.description.abstractConclusion: In a thromboembolic stroke model minocycline is neuroprotective irrespective of mouse sex and age.en_US
dc.rightsCopyright ©2011 Hoda et al; licensee BioMed Central Ltd.en_US
dc.titleSex-independent neuroprotection with minocycline after experimental thromboembolic strokeen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3287111en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameDepartment of Physiology-
dc.contributor.corporatenameDepartment of Medicine-
dc.contributor.corporatenameDepartment of Biostatistics and Epidemiology-
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy-

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