ArticleNeuropharmacology2016
GSK3β inhibition protects the immature brain from hypoxic-ischaemic insult via reduced STAT3 signalling.
Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials.Journal of neuroinflammation · 2023Pooled it
- Neuroprotection From Intracerebral Hemorrhage Following Pharmacological Inhibition of GSK3β Depends on HFE Gene Status.Journal of neurochemistry · 2026Article
- Fabrication of Lithium/Strontium-Releasing Smart Bioactive Glasses with Anti-Inflammatory and Osteogenic Effects Tailored to Pathological Stages.Macromolecular bioscience · 2025Article
- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation.Frontiers in psychiatry · 2022Article
- PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.Cell communication and signaling : CCS · 2021Article
- Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons.Neural regeneration research · 2021Article
- IL-6/STAT3 Induced Neuron Apoptosis in Hypoxia by Downregulating ATF6 Expression.Frontiers in physiology · 2021Article
- Review
- GSK3β inhibition suppresses the hepatic lipid accumulation in Schizothorax prenanti.Fish physiology and biochemistry · 2019Article
- δ-Opioid Receptor-Nrf-2-Mediated Inhibition of Inflammatory Cytokines in Neonatal Hypoxic-Ischemic Encephalopathy.Molecular neurobiology · 2019Article
- Chronic low dose of AM404 ameliorates the cognitive impairment and pathological features in hyperglycemic 3xTg-AD mice.Psychopharmacology · 2019Article
- HADC8 Inhibitor WK2-16 Therapeutically Targets Lipopolysaccharide-Induced Mouse Model of Neuroinflammation and Microglial Activation.International journal of molecular sciences · 2019Article
- Rodent Models of Developmental Ischemic Stroke for Translational Research: Strengths and Weaknesses.Neural plasticity · 2019Review
- GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice.CNS neuroscience & therapeutics · 2017Article
- Neuronal seipin knockout facilitates Aβ-induced neuroinflammation and neurotoxicity via reduction of PPARγ in hippocampus of mouse.Journal of neuroinflammation · 2016Article
- Inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) reduces neonatal hypoxic-ischaemic brain damage.Journal of neurochemistry · 2016Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxic-ischaemic (HI) injury is an important cause of neurological morbidity in neonates. HI leads to pathophysiological responses, including inflammation and oxidative stress that culminate in cell death. Activation of glycogen synthase kinase 3β (GSK3β) and the signal transducer and activator of transcription (STAT3) promotes brain inflammation. The purpose of this study was to test whether inhibition of GSK3β signalling protects against neonatal HI brain injury. Mice were subjected to HI at postnatal day (PND) 9 and treated with a selective GSK3β inhibitor, SB216763. Brain injury and caspase-3 activation, anti-oxidant and inflammatory mRNA responses and activation of STAT3 were analysed. Our results show that HI reduced phosphorylation of GSK3β, thus promoting its kinase activity. The GSK3β inhibitor reduced caspase-3 activation and neuronal cell death elicited by HI and reverted the effects of HI on gene expression of the anti-oxidant enzyme sod2 and mitochondrial factor pgc1α. The HI insult activated STAT3 in glial cells and GSK3β inhibition attenuated STAT3 phosphorylation and its nuclear translocation following HI. Further, GSK3β inhibition reduced HI-induced gene expression of pro-inflammatory cytokines tnfα and Il-6, while promoted the anti-inflammatory factor Il-10. In summary, data show that GSK3β inhibition is neuroprotective in neonatal HI brain injury likely via reduced pro-inflammatory responses by blocking STAT3 signalling. Our study suggests that pharmacological interventions built upon GSK3β silencing strategies could represent a novel therapy in neonatal brain injury.
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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.