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dc.contributor.authorAtochin, Dmitriy N.
dc.contributor.authorSchepetkin, Igor A.
dc.contributor.authorKhlebnikov, Andrei I.
dc.contributor.authorSeledtson, Victor I.
dc.contributor.authorSwanson, Helen
dc.contributor.authorQuinn, Mark T.
dc.contributor.authorHuang, Paul L.
dc.date.accessioned2016-07-07T15:14:52Z
dc.date.available2016-07-07T15:14:52Z
dc.date.issued2016-03
dc.identifier.citationAtochin, Dmitriy N. , Igor A. Schepetkin, Andrei I. Khlebnikov, Victor I. Seledtsov, Helen Swanson, Mark T. Quinn, and Paul L. Huang. "A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in mice." Neuroscience Letters 618 (April 2016): 45-49. DOI:10.1016/j.neulet.2016.02.033.en_US
dc.identifier.issn0304-3940
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/9921
dc.description.abstractThe c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30 min) with subsequent reperfusion (48 h). Mice were treated with IQ-1S (25 mg/kg) suspended in 10% solutol or with vehicle alone 30 min before and 24 h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30 min of MCAO provoked by a filament and during the first 30 min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48 h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury.en_US
dc.description.sponsorshipAmerican Heart Association Grant-in-Aid (13GRNT16930060); NIH IDeA Program Grant GM110732 (M.T.Q.)en_US
dc.titleA novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia–reperfusion injury in miceen_US
dc.typeArticleen_US
mus.citation.extentfirstpage45en_US
mus.citation.extentlastpage49en_US
mus.citation.journaltitleNeuroscience Lettersen_US
mus.citation.volume618en_US
mus.identifier.categoryEngineering & Computer Scienceen_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.doi10.1016/j.neulet.2016.02.033en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Engineeringen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.contributor.orcidQuinn, Mark T.|0000-0001-8114-5073en_US


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