Neuroglobin protects the brain from experimental stroke in vivo
Open accessAbstract
Neuroglobin (Ngb) is an O 2 -binding protein localized to cerebral neurons of vertebrates, including humans. Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport O 2 , detoxify reactive oxygen species, or serve as a hypoxia sensor. We reported recently that hypoxia stimulates transcriptional activation of Ngb in cultured cortical neurons and that antisense inhibition of Ngb expression increases hypoxic neuronal injury, whereas overexpression of Ngb confers resistance to hypoxia. These findings are consistent with a role for Ngb in promoting neuronal survival after hypoxic insults in vitro . Here we report that in rats, intracerebroventricular administration of an Ngb antisense, but not sense, oligodeoxynucleotide increases infarct volume and worsens functional neurological outcome, whereas intracerebral administration of a Ngb-expressing adeno-associated virus vector reduces infarct size and improves functional outcome, after focal cerebral ischemia induced by occlusion of the middle cerebral artery. We conclude that Ngb acts as an endogenous neuroprotective factor in focal cerebral ischemia and may therefore represent a target for the development of new treatments for stroke.
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Off-target effects for VAS2870, namely nonspecific alkylation of thiols, have been reported.
“Off-target effects for VAS2870, namely nonspecific alkylation of thiols, have been reported (915).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [915]
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- Authors
- Sun, Y., Jin, K., Peel, A., Mao, X. O., Xie, L., & Greenberg, D. A.
- Affiliations
- Buck Institute for Research on Aging (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-03-05
- Volume
- 100
- Issue
- 6
- Pages
- 3497-3500
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC152321
- OpenAlex
- W2039370814
- Cited by
- 354
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 13 · 2015: 16 · 2014: 15 · 2013: 24 · 2012: 28
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 35965, P01NS035965)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- neuroglobin, stroke, focal cerebral ischemia, neuroprotection, antisense oligodeoxynucleotides, adeno-associated virus vectors, infarct size, functional neurological outcome, middle cerebral artery occlusion, hypoxia, oxygen-binding proteins, gene therapy
- MeSH terms
- Neuroglobin, Dependovirus, Amino Acid Sequence, Animals, Brain Ischemia, Genetic Vectors, Globins, Humans, Male, Molecular Sequence Data, Nerve Tissue Proteins, Gene Expression, Rats, Sprague-Dawley, Neuroprotective Agents, Oligodeoxyribonucleotides, Antisense, Stroke, Rats, In Vitro Techniques
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