ArticleScientific reports2018
Astrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.bioRxiv : the preprint server for biology · 2026Article
- LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models.Journal of neurochemistry · 2026Article
- Quantifying White Matter Hyperintensities: Automated Volumetry Compared with Visual Grading Scales.Medicina (Kaunas, Lithuania) · 2025Article
- Heterogeneity of Astrocyte Reactivity.Annual review of neuroscience · 2025Review
- A single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation: focus on the glial response.Pharmacological reports : PR · 2025Article
- Epigallocatechin-3-Gallate Inhibits Oxidative Stress Through the Keap1/Nrf2 Signaling Pathway to Improve Alzheimer Disease.Molecular neurobiology · 2025Review
- Multitarget Effects of Nrf2 Signalling in the Brain: Common and Specific Functions in Different Cell Types.Antioxidants (Basel, Switzerland) · 2024Review
- Dynamic Neuro-Glial-Vascular Responses in a Mouse Model of Vascular Cognitive Impairment.Neuroglia (Basel, Switzerland) · 2024Article
- A phenotypic screening platform for identifying chemical modulators of astrocyte reactivity.Nature neuroscience · 2024Article
- The cell-specific roles of Nrf2 in acute and chronic phases of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration.Nature communications · 2023Article
- Sulforaphane promotes white matter plasticity and improves long-term neurological outcomes after ischemic stroke via the Nrf2 pathway.Free radical biology & medicine · 2022Article
- P301S-hTau acetylates KEAP1 to trigger synaptic toxicity via inhibiting NRF2/ARE pathway: A novel mechanism underlying hTau-induced synaptic toxicities.Clinical and translational medicine · 2022Article
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- Nox2 underpins microvascular inflammation and vascular contributions to cognitive decline.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Good, bad, and neglectful: Astrocyte changes in neurodegenerative disease.Free radical biology & medicine · 2022Review
- The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Mouse models have shown that cerebral hypoperfusion causes white matter disruption and memory impairment relevant to the study of vascular cognitive impairment and dementia. The associated mechanisms include inflammation and oxidative stress are proposed to drive disruption of myelinated axons within hypoperfused white matter. The aim of this study was to determine if increased endogenous anti-oxidant and anti-inflammatory signalling in astrocytes was protective in a model of mild cerebral hypoperfusion. Transgenically altered mice overexpressing the transcription factor Nrf2 (GFAP-Nrf2) and wild type littermates were subjected to bilateral carotid artery stenosis or sham surgery. Behavioural alterations were assessed using the radial arm maze and tissue was collected for pathology and transcriptome analysis six weeks post-surgery. GFAP-Nrf2 mice showed less pronounced behavioural impairments compared to wild types following hypoperfusion, paralleled by reduced optic tract white matter disruption and astrogliosis. There was no effect of hypoperfusion on anti-oxidant gene alterations albeit the levels were increased in GFAP-Nrf2 mice. Instead, pro-inflammatory gene expression was determined to be significantly upregulated in the optic tract of hypoperfused wild type mice but differentially affected in GFAP-Nrf2 mice. In particular, complement components (C4 and C1q) were increased in wild type hypoperfused mice but expressed at levels similar to controls in hypoperfused GFAP-Nrf2 mice. This study provides evidence that overexpression of Nrf2 in astrocytes exerts beneficial effects through repression of inflammation and supports the potential use of Nrf2-activators in the amelioration of cerebrovascular-related inflammation and white matter degeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.