ArticleCNS neuroscience & therapeutics2017
GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice.
Article in CNS neuroscience & therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
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- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
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- GSK-3β Allosteric Inhibition: A Dead End or a New Pharmacological Frontier?International journal of molecular sciences · 2023Review
- New insights into the role of GSK-3β in the brain: from neurodegenerative disease to tumorigenesis.PeerJ · 2023Review
- Identification of Potential Kinase Inhibitors within the PI3K/AKT Pathway ofBiomolecules · 2021Article
- The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status.Journal of neuroinflammation · 2021Review
- TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury.Translational stroke research · 2021Article
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- Apigenin-7-Aging · 2020Article
- Hypoxic-ischemic-related cerebrovascular changes and potential therapeutic strategies in the neonatal brain.Journal of neuroscience research · 2020Review
- The Role of Mitochondrial and Endoplasmic Reticulum Reactive Oxygen Species Production in Models of Perinatal Brain Injury.Antioxidants & redox signaling · 2019Article
- The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer's disease.Neurochemistry international · 2019Article
- Brain-selective mild hypothermia promotes long-term white matter integrity after ischemic stroke in mice.CNS neuroscience & therapeutics · 2018Article
- Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A.Neurobiology of disease · 2018Article
- The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia.Acta pharmacologica Sinica · 2018Review
- Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo.Acta pharmacologica Sinica · 2018Article
- Global transcriptomic analysis suggests carbon dioxide as an environmental stressor in spaceflight: A systems biology GeneLab case study.Scientific reports · 2018Article
- GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice.CNS neuroscience & therapeutics · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGlycogen synthase kinase 3β (GSK-3β) is activated following hypoxic-ischemic (HI) brain injury. TDZD-8 is a specific GSK-3β inhibitor. Currently, the impact of inhibiting GSK-3β in neonatal HI injury is unknown. We aimed to investigate the effect of TDZD-8 following neonatal HI brain injury.
methodsUnilateral common carotid artery ligation followed by hypoxia was used to induce HI injury in postnatal day 7 mouse pups pretreated with TDZD-8 or vehicle. The infarct volume, whole-brain imaging, Nissl staining, and behavioral tests were used to evaluate the protective effect of TDZD-8 on the neonatal brain and assess functional recovery after injury. Western blot was used to evaluate protein levels of phosphorylated protein kinase B (Akt), GSK-3β, and cleaved caspase-3. Protein levels of cleaved caspase-3, neuronal marker, and glial fibrillary acidic protein were detected through immunohistochemistry.
resultsPretreatment with TDZD-8 significantly reduced brain damage and improved neurobehavioral outcomes following HI injury. TDZD-8 reversed the reduction of phosphorylated Akt and GSK-3β, and the activation of caspase-3 induced by hypoxia-ischemia. In addition, TDZD-8 suppressed apoptotic cell death and reduced reactive astrogliosis.
conclusionTDZD-8 has the therapeutic potential for hypoxic-ischemic brain injury in neonates. The neuroprotective effect of TDZD-8 appears to be mediated through its antiapoptotic activity and by reducing astrogliosis.
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