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<a href="http://doi.org/10.1007/s11095-021-03046-4" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s11095-021-03046-4</a>
ISSN
1573-904X
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Update Year & Number
May 2021 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
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Title
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The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.
Publisher
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Pharmaceutical Research
Date
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2021
2021-05-12
Subject
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Bioenergetics; CDGSH; iron-sulfur; OXPHOS; PAMPA; t-MCAO
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Saralkar P; Mdzinarishvili A; Arsiwala TA; Lee Y; Sullivan PG; Pinti MV; Hollander JM; Kelley EE; Ren X; Hu H; Simpkins J; Brown C; Hazlehurst LE; Huber JD; Geldenhuys WJ
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Purpose: Therapeutic strategies to treat ischemic stroke are limited due to the heterogeneity of cerebral ischemic injury and the mechanisms that contribute to the cell death. Since oxidative stress is one of the primary mechanisms that cause brain injury post-stroke, we hypothesized that therapeutic targets that modulate mitochondrial function could protect against reperfusion-injury after cerebral ischemia, with the focus here on a mitochondrial protein, mitoNEET, that modulates cellular bioenergetics.; Method: In this study, we evaluated the pharmacology of the mitoNEET ligand NL-1 in an in vivo therapeutic role for NL-1 in a C57Bl/6 murine model of ischemic stroke.; Results: NL-1 decreased hydrogen peroxide production with an IC 50 of 5.95 μM in neuronal cells (N2A). The in vivo activity of NL-1 was evaluated in a murine 1 h transient middle cerebral artery occlusion (t-MCAO) model of ischemic stroke. We found that mice treated with NL-1 (10 mg/kg, i.p.) at time of reperfusion and allowed to recover for 24 h showed a 43% reduction in infarct volume and 68% reduction in edema compared to sham-injured mice. Additionally, we found that when NL-1 was administered 15 min post-t-MCAO, the ischemia volume was reduced by 41%, and stroke-associated edema by 63%.; Conclusion: As support of our hypothesis, as expected, NL-1 failed to reduce stroke infarct in a permanent photothrombotic occlusion model of stroke. This report demonstrates the potential therapeutic benefits of using mitoNEET ligands like NL-1 as novel mitoceuticals for treating reperfusion-injury with cerebral stroke.
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<a href="http://doi.org/10.1007/s11095-021-03046-4" target="_blank" rel="noreferrer noopener">10.1007/s11095-021-03046-4</a>
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journalArticle
2021
Arsiwala TA
Bioenergetics
Brown C
CDGSH
Department of Integrative Medical Sciences
Geldenhuys WJ
Hazlehurst LE
Hollander JM
Hu H
Huber JD
iron-sulfur
journalArticle
Kelley EE
Lee Y
May 2021 List
Mdzinarishvili A
NEOMED College of Medicine
OXPHOS
PAMPA
Pharmaceutical research
Pinti MV
Ren X
Saralkar P
Simpkins J
Sullivan PG
t-MCAO