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Docosanoids Promote Neurogenesis and Angiogenesis, Blood-Brain Barrier Integrity, Penumbra Protection, and Neurobehavioral Recovery After Experimental Ischemic Stroke
Open accessAbstract
Docosahexaenoic acid (DHA) and neuroprotectin D1 (NPD1) are neuroprotective after experimental ischemic stroke. To explore underlying mechanisms, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo) and treated with DHA (5 mg/kg, IV) or NPD1 (5 μg/per rat, ICV) and vehicles 1 h after. Neuro-behavioral assessments was conducted on days 1, 2, and 3, and on week 1, 2, 3, or 4. BrdU was injected on days 4, 5, and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7, and lipidomic analysis at 4 and 5 h after onset of stroke. DHA improved short- and long-term behavioral functions and reduced cortical, subcortical, and total infarct volumes (by 42, 47, and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU+/Ki-67+, BrdU+/DCX+, and BrdU+/NeuN+ cells in the cortex, subventricular zone, and dentate gyrus and potentiated NPD1 synthesis in the penumbra at 5 h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71-positive cells and vessels, axonal regeneration in the penumbra, and attenuated blood-brain barrier (BBB) after MCAo. We conclude that docosanoid administration increases neurogenesis and angiogenesis, activates NPD1 synthesis in the penumbra, and diminishes BBB permeability, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
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Metadata
- Authors
- Belayev, L., Hong, S.-H., Menghani, H., Marcell, S. J., Obenaus, A., Freitas, R. S., Khoutorova, L., Balaszczuk, V., Jun, B., Oriá, R. B., & Bazan, N. G.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Belayev, Ludmila
- Venue
- Molecular Neurobiology
- Published
- 2018-06-01
- Volume
- 55
- Issue
- 8
- Pages
- 7090-7106
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- PMC
- PMC6054805
- OpenAlex
- W2807382073
- Cited by
- 103
- References
- 62
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 13 · 2023: 13 · 2022: 15 · 2021: 17 · 2020: 17 · 2019: 6 · 2018: 1
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (NS046741)
- National Institute of General Medical Sciences (GM103340)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- docosanoids, docosahexaenoic acid, neuroprotectin D1, ischemic stroke, neurogenesis, angiogenesis, blood-brain barrier integrity, neurobehavioral recovery, middle cerebral artery occlusion, infarct size, axon regeneration, subventricular zone, dentate gyrus, lipidomics
- MeSH terms
- Doublecortin Protein, Animals, Axons, Behavior, Animal, Blood-Brain Barrier, Brain Ischemia, Docosahexaenoic Acids, Fatty Acids, Male, Nerve Regeneration, Permeability, Survival Analysis, Rats, Sprague-Dawley, Neovascularization, Physiologic, Infarction, Middle Cerebral Artery, Stroke, Neurogenesis
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