Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice
dc.contributor.author | Bhuiyan, MIH | |
dc.contributor.author | Fischer, S | |
dc.contributor.author | Patel, SM | |
dc.contributor.author | Oft, H | |
dc.contributor.author | Zhang, T | |
dc.contributor.author | Foley, LM | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Hitchens, TK | |
dc.contributor.author | Molyneaux, BJ | |
dc.contributor.author | Deng, X | |
dc.contributor.author | Sun, D | |
dc.date.accessioned | 2022-11-17T12:23:11Z | |
dc.date.issued | 2022-11-11 | |
dc.date.updated | 2022-11-17T10:29:00Z | |
dc.description.abstract | SPAK inhibitor ZT-1a was previously shown to be neuroprotective in murine ischemic stroke models. In this study, we further examined the efficacy of four ZT-1a derivatives (ZT-1c, -1d, -1g and -1h) on reducing stroke-induced sensorimotor function impairment and brain lesions. Vehicle control (Veh) or ZT-1 derivatives were administered via osmotic pump to adult C57BL/6J mice during 3–21 h post-stroke. Neurological behavior of these mice was assessed at days 1, 3, 5, and 7 post-stroke and MRI T2WI and DTI analysis was subsequently conducted in ex vivo brains. Veh-treated stroke mice displayed sensorimotor function deficits compared to Sham mice. In contrast, mice receiving ZT-1a derivatives displayed significantly lower neurological deficits at days 3–7 post-stroke (p < 0.05), with ZT-1a, ZT-1c and ZT-1d showing greater impact than ZT-1h and ZT-1g. ZT-1a treatment was the most effective in reducing brain lesion volume on T2WI and in preserving NeuN + neurons (p < 0.01), followed by ZT-1d > -1c > -1g > -1h. The Veh-treated stroke mice displayed white matter tissue injury, reflected by reduced fractional anisotropy (FA) or axial diffusivity (AD) values in external capsule, internal capsule and hippocampus. In contrast, only ZT-1a-as well as ZT-1c-treated stroke mice exhibited significantly higher FA and AD values. These findings demonstrate that post-stroke administration of SPAK inhibitor ZT-1a and its derivatives (ZT-1c and ZT-1d) is effective in protecting gray and white matter tissues in ischemic brains, showing a potential for ischemic stroke therapy development. | en_GB |
dc.description.sponsorship | Veteran Affairs | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.format.extent | 105441- | |
dc.identifier.citation | Article 105441 | en_GB |
dc.identifier.doi | https://doi.org/10.1016/j.neuint.2022.105441 | |
dc.identifier.grantnumber | VA I01BX002891-01A1 | en_GB |
dc.identifier.grantnumber | IK6 BX005647 | en_GB |
dc.identifier.grantnumber | R01 NS166199-01A1 | en_GB |
dc.identifier.grantnumber | IEC\NSFC\201094 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/131797 | |
dc.identifier | ORCID: 0000-0001-8683-509X (Zhang, Jinwei) | |
dc.identifier | ScopusID: 24385918800 (Zhang, Jinwei) | |
dc.identifier | ResearcherID: N-8584-2017 | Q-7959-2019 (Zhang, Jinwei) | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights.embargoreason | Under embargo until 11 November 2023 in compliance with publisher policy | en_GB |
dc.rights | © 2022 Published by Elsevier Ltd. This version is made available under the CC-BY-NC-ND 4.0 license: https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dc.subject | DTI | en_GB |
dc.subject | Ischemic stroke | en_GB |
dc.subject | MRI | en_GB |
dc.subject | Neurodegeneration | en_GB |
dc.subject | SPAK | en_GB |
dc.title | Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-11-17T12:23:11Z | |
dc.identifier.issn | 0197-0186 | |
exeter.article-number | 105441 | |
dc.description | This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record | en_GB |
dc.description | Data availability: Data will be made available on request. | en_GB |
dc.identifier.journal | Neurochemistry International | en_GB |
dc.relation.ispartof | Neurochemistry International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2022-11-08 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2022-11-11 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-11-17T12:18:18Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2022-11-11T00:00:00Z | |
refterms.panel | A | en_GB |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2022 Published by Elsevier Ltd. This version is made available under the CC-BY-NC-ND 4.0 license: https://creativecommons.org/licenses/by-nc-nd/4.0/