The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.
Title
The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.
Creator
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
Publisher
Pharmaceutical Research
Date
2021
2021-05-12
Description
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.
Subject
Bioenergetics; CDGSH; iron-sulfur; OXPHOS; PAMPA; t-MCAO
Identifier
Rights
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Format
journalArticle
URL Address
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ISSN
1573-904X
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
Update Year & Number
May 2021 List
Citation
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, “The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.,” NEOMED Bibliography Database, accessed April 27, 2024, https://neomed.omeka.net/items/show/11676.