ArticleJournal of neuroinflammation2019
Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 111 citations in OpenAlex.
- A cell motility-based selective hydrogel enables rapid generation of nerve-repairing blood clots.Bioactive materials · 2026Article
- Myeloid Cell-Specific Retinoid X Receptor Signaling Facilitates White Matter Repair and Stroke Recovery in Aged Mice.Stroke · 2026Article
- Brain Single-Cell Transcriptional Responses to Bexarotene-Activated RXR in an Alzheimer's Disease Model.International journal of molecular sciences · 2026Article
- NEO1 modulates the A1 astrocyte polarization in subarachnoid hemorrhage through the cPLA2-MAVS signaling pathway.Journal of neuroinflammation · 2025Article
- PAI-1 in Skin Malignancies: a Central Regulator of Tumor Progression and Therapeutic Resistance.Current treatment options in oncology · 2025Review
- Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition.Biomolecules · 2025Review
- Deacetylase SIRT2 Inhibition Promotes Microglial M2 Polarization Through Axl/PI3K/AKT to Alleviate White Matter Injury After Subarachnoid Hemorrhage.Translational stroke research · 2025Article
- Bexarotene Promotes Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neurons with Decreased Proliferation.Molecular neurobiology · 2025Article
- Role of Nuclear Receptors on the Progression of Multiple Sclerosis: A Review.Cellular and molecular neurobiology · 2025Review
- Retinoid X receptor agonist 9CDHRA mitigates retinal ganglion cell apoptosis and neuroinflammation in a mouse model of glaucoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Research progress of early brain Injury in subarachnoid hemorrhage from 2004 to 2024: a bibliometric analysis.Neurosurgical review · 2025Review
- Sirtuins as Potential Targets for Neuroprotection: Mechanisms of Early Brain Injury Induced by Subarachnoid Hemorrhage.Translational stroke research · 2024Review
- PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.Journal of neuroinflammation · 2024Article
- GW0742 reduces mast cells degranulation and attenuates neurological impairments via PPARExperimental neurology · 2024Article
- Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- FGF21 alleviates endothelial mitochondrial damage and prevents BBB from disruption after intracranial hemorrhage through a mechanism involving SIRT6.Molecular medicine (Cambridge, Mass.) · 2023Article
- Perampanel attenuates oxidative stress and pyroptosis following subarachnoid hemorrhage via the SIRT3/FOXO3α pathway.Scientific reports · 2023Article
- Sinomenine Protects against Early Brain Injury by Inhibiting Microglial Inflammatory Response via Nrf2-Dependent Pathway after Subarachnoid Hemorrhage.Brain sciences · 2023Article
- CNS-peripheral immune interactions in hemorrhagic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Brain nuclear receptors and cardiovascular function.Cell & bioscience · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSubarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities. Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury. This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH.
methodsTwo hundred male Sprague-Dawley rats were used. The endovascular perforation induced SAH. Bexarotene was administered intraperitoneally at 1 h after SAH induction. To investigate the underlying mechanism, the selective RXR antagonist UVI3003 and RXR siRNA or SIRT6 inhibitor OSS128167 was administered via intracerebroventricular 1 h before SAH induction. Post-SAH assessments including SAH grade, neurological score, brain water content, Western blot, and immunofluorescence were performed.
resultsThe endogenous RXR and sirtuin 6 (SIRT6) protein levels were increased after SAH. Bexarotene treatment significantly reduced brain edema and improved the short-/long-term neurological deficit after SAH. Mechanistically, bexarotene increased the levels of PPARγ and SIRT6; decreased the expression of phosphorylated FoxO3a (p-FoxO3a), IL-6, IL-1β, and TNF-a; and inhibited the microglia activation and neutrophils infiltration at 24 h after SAH. Either UVI3003, OSS128167, or RXR siRNA abolished the neuroprotective effects of bexarotene and its regulation on protein levels of PPARγ/SIRT6/p-FoxO3a after SAH.
conclusionsThe activation of RXR by bexarotene attenuated neuroinflammation and improved neurological deficits after SAH. The anti-neuroinflammatory effect was at least partially through regulating PPARγ/SIRT6/FoxO3a pathway. Bexarotene may be a promising therapeutic strategy in the management of SAH patients.
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