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dc.contributor.authorMatsukawa, Noriyuki
dc.contributor.authorYasuhara, Takao
dc.contributor.authorHara, Koichi
dc.contributor.authorXu, Lin
dc.contributor.authorMaki, Mina
dc.contributor.authorYu, Guolong
dc.contributor.authorKaneko, Yuji
dc.contributor.authorOjika, Kosei
dc.contributor.authorHess, David C.
dc.contributor.authorBorlongan, Cesar V
dc.date.accessioned2010-09-24T22:03:27Z
dc.date.available2010-09-24T22:03:27Z
dc.date.issued2009-10-19en_US
dc.identifier.citationBMC Neurosci. 2009 Oct 6; 10:126en_US
dc.identifier.issn1471-2202en_US
dc.identifier.pmid19807907en_US
dc.identifier.doi10.1186/1471-2202-10-126en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/144
dc.description.abstractBACKGROUND: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. RESULTS: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. CONCLUSION: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAdenosine Triphosphate / metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnoxiaen_US
dc.subject.meshApoptosis / drug effectsen_US
dc.subject.meshAstrocytes / cytology / drug effects / metabolismen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Counten_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCorpus Striatum / cytology / drug effects / metabolismen_US
dc.subject.meshCytochromes c / metabolismen_US
dc.subject.meshCytoprotectionen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGlucose / deficiencyen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshIn Situ Nick-End Labelingen_US
dc.subject.meshInfarction, Middle Cerebral Artery / drug therapy / metabolism / physiopathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMinocycline / pharmacology / therapeutic useen_US
dc.subject.meshMotor Skills / drug effectsen_US
dc.subject.meshNeurons / cytology / drug effects / metabolismen_US
dc.subject.meshNeuroprotective Agents / pharmacology / therapeutic useen_US
dc.subject.meshProto-Oncogene Proteins c-bcl-2 / metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.titleTherapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2762982en_US
dc.contributor.corporatenameDepartment of Neurologyen_US
refterms.dateFOA2019-04-09T16:27:07Z
html.description.abstractBACKGROUND: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. RESULTS: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. CONCLUSION: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.


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