ArticleMolecular neurobiology2023
The Aldose Reductase Inhibitor Epalrestat Maintains Blood-Brain Barrier Integrity by Enhancing Endothelial Cell Function during Cerebral Ischemia.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Aldose reductase inhibition suppresses microglial endoplasmic reticulum stress and ferritinophagy in ischemic stroke.Acta pharmacologica Sinica · 2026Article
- Insights into the potential pathogenesis and therapeutic implications of ferroptosis in brain microvascular endothelial cells during stroke.Frontiers in immunology · 2026Review
- Endothelial Glycocalyx Degradation as a Mediator of Neuroinflammation and Cognitive Impairment in Aged Rats: Protective Role of SS-31.Molecular neurobiology · 2025Article
- Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review).International journal of molecular medicine · 2025Review
- Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic therapy resistance in hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- NX210c drug candidate peptide strengthens mouse and human blood-brain barriers.Fluids and barriers of the CNS · 2024Article
- Diabetic neuropathy: A NRF2 disease?Journal of diabetes · 2024Review
- An Update on the Study of the Molecular Mechanisms Involved in Autophagy during Bacterial Pathogenesis.Biomedicines · 2024Review
- Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.BMC medicine · 2024Article
- Akt/mTOR Pathway Agonist SC79 Inhibits Autophagy and Apoptosis of Oligodendrocyte Precursor Cells Associated with Neonatal White Matter Dysplasia.Neurochemical research · 2024Article
- Bioactive Materials Facilitate the Restoration of Neurological Function Post Cerebral Ischemic Stroke.International journal of nanomedicine · 2024Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Excessive activation of aldose reductase (AR) in the brain is a risk factor for aggravating cerebral ischemia injury. Epalrestat is the only AR inhibitor with proven safety and efficacy, which is used in the clinical treatment of diabetic neuropathy. However, the molecular mechanisms underlying the neuroprotection of epalrestat remain unknown in the ischemic brain. Recent studies have found that blood-brain barrier (BBB) damage was mainly caused by increased apoptosis and autophagy of brain microvascular endothelial cells (BMVECs) and decreased expression of tight junction proteins. Thus, we hypothesized that the protective effect of epalrestat is mainly related to regulating the survival of BMVECs and tight junction protein levels after cerebral ischemia. To test this hypothesis, a mouse model of cerebral ischemia was established by permanent middle cerebral artery ligation (pMCAL), and the mice were treated with epalrestat or saline as a control. Epalrestat reduced the ischemic volume, enhanced BBB function, and improved the neurobehavior after cerebral ischemia. In vitro studies revealed that epalrestat increased the expression of tight junction proteins, and reduced the levels of cleaved-caspase3 and LC3 proteins in mouse BMVECs (bEnd.3 cells) exposed to oxygen-glucose deprivation (OGD). In addition, bicalutamide (an AKT inhibitor) and rapamycin (an mTOR inhibitor) increased the epalrestat-induced reduction in apoptosis and autophagy related protein levels in bEnd.3 cells with OGD treatment. Our findings suggest that epalrestat improves BBB function, which may be accomplished by reducing AR activation, promoting tight junction proteins expression, and upregulating AKT/mTOR signaling pathway to inhibit apoptosis and autophagy in BMVECs.
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