AR-A014418 as a glycogen synthase kinase-3 inhibitor: Anti-apoptotic and therapeutic potential in experimental spinal cord injury

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dc.authorid0000-0002-5300-4449en_US
dc.contributor.authorTuncdemir, Matem
dc.contributor.authorYildirim, Aziz
dc.contributor.authorKaraoglan, Alper
dc.contributor.authorAkdemir, Osman
dc.contributor.authorOzturk, Melek
dc.date.accessioned2024-07-12T21:52:26Z
dc.date.available2024-07-12T21:52:26Z
dc.date.issued2013en_US
dc.departmentMaltepe Üniversitesien_US
dc.description.abstractObjectives: We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. Materials and methods: In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. Results: In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p<0.05, p<0.01), were significantly decreased compared to the trauma groups, as were the levels of bax (p<0.01) and TGF-beta 1 immunoreactivity. Results of the locomotor test were significantly increased in the treatment group (p<0.001) as compared to the trauma group. Conclusions: In this experimental spinal cord trauma model study neural apoptosis was significantly triggered in secondary damage developed after trauma, however, neurological healing was expedited by preventing mitochondrial apoptosis and reducing the inflammation by the potent inhibitor AR-A014418, which is GSK-3beta selective. 2011 Sociedad Espanola de Neurocirugia. Published by Elsevier Espana, S.L. All rights reserved.en_US
dc.description.sponsorshipScientific Research Projects Coordination Unit of Istanbul University [UDP-17368]en_US
dc.description.sponsorshipThis work was supported by Scientific Research Projects Coordination Unit of Istanbul University, project number UDP-17368.en_US
dc.identifier.doi10.1016/j.neucir.2011.12.006
dc.identifier.endpage32en_US
dc.identifier.issn1130-1473
dc.identifier.issue1en_US
dc.identifier.pmid23116585en_US
dc.identifier.scopus2-s2.0-84875450571en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage22en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.neucir.2011.12.006
dc.identifier.urihttps://hdl.handle.net/20.500.12415/8368
dc.identifier.volume24en_US
dc.identifier.wosWOS:000315752400004en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherELSEVIER DOYMA SLen_US
dc.relation.ispartofNEUROCIRUGIAen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKY03091
dc.subjectSpinal cord injuryen_US
dc.subjectGSK-3betaen_US
dc.subjectAR-A014418en_US
dc.subjectApoptosisen_US
dc.subjectTGF-betaen_US
dc.titleAR-A014418 as a glycogen synthase kinase-3 inhibitor: Anti-apoptotic and therapeutic potential in experimental spinal cord injuryen_US
dc.typeArticle
dspace.entity.typePublication

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