ArticleMolecular neurobiology2023
tDCS Regulates ASBT-3-OxoLCA-PLOD2-PTEN Signaling Pathway to Confer Neuroprotection Following Rat Cerebral Ischemia-Reperfusion Injury.
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 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Gut Microbiota and Ischemic Stroke: From Pre-Stroke Dysbiosis and Acute-Phase Changes to Therapeutic Applications.Brain and behavior · 2026Review
- Ischemic stroke triggers brain-wide synaptic remodeling within four hours.PLoS biology · 2026Article
- Dual-tDCS Ameliorates Cerebral Injury and Promotes Motor Function Recovery via cGAS-STING Signaling Pathway in a Rat Model of Ischemic Stroke.Molecular neurobiology · 2025Article
- Anti-inflammatory effect of curcumin on neurological disorders: a narrative review.Frontiers in pharmacology · 2025Review
- Icariin inhibits apoptosis in OGD-induced neurons by regulating M2 pyruvate kinase.IBRO neuroscience reports · 2024Article
- Itaconate alleviates anesthesia/surgery-induced cognitive impairment by activating a Nrf2-dependent anti-neuroinflammation and neurogenesis via gut-brain axis.Journal of neuroinflammation · 2024Article
- Bibliometric analysis of PTEN in neurodevelopment and neurodegeneration.Frontiers in aging neuroscience · 2024Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Humans exhibit a rich intestinal microbiome that contain high levels of bacteria capable of producing 3-oxo-lithocholic acid (3-oxoLCA) and other secondary bile acids (BAs). The molecular mechanism mediating the role of 3-oxoLCA in cerebral ischemia-reperfusion (I/R) injury remains unclear. We investigated the role of 3-oxoLCA in a rat cerebral I/R injury model. We found that the concentrations of 3-oxoLCA within the cerebrospinal fluid were increased following I/R. In the in vitro oxygen-glucose deprivation (OGD) model, the levels of intraneuronal 3-oxoLCA was elevated following OGD insult. We showed that the increase of membrane ASBT (apical sodium-dependent bile acid transporter) contributed to OGD-induced elevation of intraneuronal 3-oxoLCA. Increasing intraneuronal 3-oxoLCA promoted ischemia-induced neuronal death, whereas reducing 3-oxoLCA levels were neuroprotective. Our results revealed that PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenases 2) functioned upstream of PTEN (the phosphatase and tensin homolog deleted on chromosome 10) and downstream of 3-oxoLCA to promote OGD-induced neuronal injury. We further demonstrated that direct-current stimulation (DCS) decreased the levels of intraneuronal 3-oxoLCA and membrane ASBT in OGD-insulted neurons, while bilateral transcranial DCS (tDCS) reduced brain infarct volume following I/R by inhibiting ASBT. Together, these data suggest that increased expression of ASBT promotes neuronal death via 3-oxoLCA-PLOD2-PTEN signaling pathway. Importantly, bilateral tDCS suppresses ischemia-induced increase of ASBT, thereby conferring neuroprotection after cerebral I/R injury.
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