ArticleMolecular neurobiology2016
Insulin Receptor Substrate-1 Activation Mediated p53 Downregulation Protects Against Hypoxic-Ischemia in the Neonatal Brain.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Review of Associations of Diabetes and Insulin Resistance With Brain Health in Three Harmonised Cohort Studies of Ageing and Dementia.Diabetes/metabolism research and reviews · 2025Review
- Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation.Journal of ginseng research · 2023Article
- Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly.Cell death discovery · 2021Article
- Brain insulin signaling and cerebrovascular disease in human postmortem brain.Acta neuropathologica communications · 2021Article
- Early neuroimaging and ultrastructural correlates of injury outcome after neonatal hypoxic-ischaemia.Brain communications · 2021Article
- Early Blood Biomarkers Distinguish Inflammation from Neonatal Hypoxic-Ischemia Encephalopathy.Neurochemical research · 2020Article
- Hypoxia-Preconditioned Human Umbilical Vein Endothelial Cells Protect Against Neurovascular Damage After Hypoxic Ischemia in Neonatal Brain.Molecular neurobiology · 2018Article
- Inhibiting aberrant p53-PUMA feedback loop activation attenuates ischaemia reperfusion-induced neuroapoptosis and neuroinflammation in rats by downregulating caspase 3 and the NF-κB cytokine pathway.Journal of neuroinflammation · 2018Article
- Early Activation of Phosphatidylinositol 3-Kinase after Ischemic Stroke Reduces Infarct Volume and Improves Long-Term Behavior.Molecular neurobiology · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study determined if dietary restriction (DR) protects against hypoxic-ischemia (HI) in the neonatal brain via insulin receptor substrate-1 (IRS-1)/Akt pathway-mediated downregulation of p53 in the neurovascular unit. On postnatal (P) day 7, HI was induced in rat pups grouped from P1 into normal litter size (NL, 12 pups/dam) and increased litter size (DR, 18 pups/dam). In vivo IRS-1 anti-sense oligonucleotide and IRS-1 overexpressed recombinant adenovirus were given, and neurovascular damage was assessed. In vitro models of oxygen-glucose deprivation (OGD) examined the inhibition and overexpression of IRS-1 on p53 and cell death in neurons and endothelial cells. Compared to NL pups, DR pups had significantly higher IRS-1, p-IRS-1, and pAkt levels, decreased p53, more tight junction proteins, reduced blood-brain barrier (BBB) damage after HI, and less infarct volumes at P21. Immunofluorescence revealed that IRS-1 was upregulated in the endothelial cells and neurons of DR pups. IRS-1 downregulation in DR pups reduced p-Akt, increased p53, worsened BBB damage, and increased brain injury, whereas IRS-1 overexpression in NL pups upregulated p-Akt, decreased p53, attenuated BBB damage, and decreased brain injury. In vitro, IRS-1 downregulation aggravated cell death in neurons and endothelial cells and is associated with decreased p-Akt and increased p53. In contrast, IRS-1 overexpression reduced cell death in endothelial cells with increased p-Akt and decreased p53. In conclusion, DR reduces neurovascular damage after HI in the neonatal brain through an IRS-1/Akt-mediated p53 downregulation, suggesting that IRS-1 signaling is a therapeutic target for hypoxic brain injury in neonates.
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