A type-II positive allosteric modulator of α7 nAChRs reduces brain Injury and Improves neurological function after focal cerebral ischemia in rats

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dc.contributor.authorSun, Fen
dc.contributor.authorJin, Kunlin
dc.contributor.authorUteshev, Victor
dc.date.accessioned2019-09-12T14:26:34Z
dc.date.available2019-09-12T14:26:34Z
dc.date.issued2013
dc.description.abstractIn the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke.
dc.description.sponsorshipThis study was supported by the National Institutes of Health Grant DK-082625 and the Start-Up funds from UNTHSC to V.V. Uteshev. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.identifier.citationSun F, Jin K, Uteshev VV. A type-II positive allosteric modulator of a7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats. PLoS ONE. 2013;8(8)
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29671
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0073581
dc.publisherPLoS ONE
dc.subject.meshBrain Ischemia, therapy
dc.subject.meshStroke, therapy
dc.subject.meshReceptors, Nicotinic
dc.subject.meshAllosteric Regulation
dc.subject.meshCholinergic Agents
dc.titleA type-II positive allosteric modulator of α7 nAChRs reduces brain Injury and Improves neurological function after focal cerebral ischemia in rats
dc.typeArticle

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