ArticleAutophagy2014
Involvement of autophagy in hypoxic-excitotoxic neuronal death.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
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- Bone marrow-derived mesenchymal stem cells for ischemic stroke: mechanisms, delivery strategies, clinical evidence, and translational challenges.Stem cell research & therapy · 2026Review
- Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.Pharmacological reports : PR · 2026Article
- A Novel Approach of Development of Robust Animal Model for Autism Spectrum Disorder.Annals of neurosciences · 2026Article
- Inhibition of PTEN nuclear translocation by peptide Tat-K13 attenuates p-JUN-SESN2-AMPK-dependent autophagy and enhances neurological recovery after neonatal hypoxic-ischemic brain damage.Cell & bioscience · 2026Article
- Polydatin for treating spinal cord injury: Multiple mechanisms and challenges.Journal of pharmaceutical analysis · 2026Review
- Peiminine-Induced Selective Autophagy of AIM2 Inflammasomes Rescues Cerebral Ischemic Injury.Journal of the American Heart Association · 2026Article
- Autophagy in ischemic stroke: pathophysiology, therapeutics, and challenges ahead.Frontiers in stroke · 2026Review
- Roles for Exosomes from Various Cellular Sources in Spinal Cord Injury.Molecular neurobiology · 2025Review
- The elucidation of the dual role of Beclin-1 in ischemic stroke through systems biology modeling.iScience · 2025Article
- Closed-loop rehabilitation of upper-limb dyskinesia after stroke: from natural motion to neuronal microfluidics.Journal of neuroengineering and rehabilitation · 2025Review
- Bone marrow mesenchymal stem cells alleviate neurological dysfunction by reducing autophagy damage via downregulation of SYNPO2 in neonatal hypoxic-ischemic encephalopathy rats.Cell death & disease · 2025Article
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
- Review
- Neuronal autosis is NaCell death & disease · 2024Article
- Crosstalk among Reactive Oxygen Species, Autophagy and Metabolism in Myocardial Ischemia and Reperfusion Stages.Aging and disease · 2024Review
- Chaperones vs. oxidative stress in the pathobiology of ischemic stroke.Frontiers in molecular neuroscience · 2024Review
- N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats.Cell death & disease · 2023Article
- Biomolecular mechanisms of epileptic seizures and epilepsy: a review.Acta epileptologica · 2023Review
- The Role of Circular RNAs in Ischemic Stroke.Neurochemical research · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal autophagy is increased in numerous excitotoxic conditions including neonatal cerebral hypoxia-ischemia (HI). However, the role of this HI-induced autophagy remains unclear. To clarify this role we established an in vitro model of excitotoxicity combining kainate treatment (Ka, 30 µM) with hypoxia (Hx, 6% oxygen) in primary neuron cultures. KaHx rapidly induced excitotoxic death that was completely prevented by MK801 or EGTA. KaHx also stimulated neuronal autophagic flux as shown by a rise in autophagosome number (increased levels of LC3-II and punctate LC3 labeling) accompanied by increases in lysosomal abundance and activity (increased SQSTM1/p62 degradation, and increased LC3-II levels in the presence of lysosomal inhibitors) and fusion (shown using an RFP-GFP-LC3 reporter). To determine the role of the enhanced autophagy we applied either pharmacological autophagy inhibitors (3-methyladenine or pepstatinA/E64) or lentiviral vectors delivering shRNAs targeting Becn1 or Atg7. Both strategies reduced KaHx-induced neuronal death. A prodeath role of autophagy was also confirmed by the enhanced toxicity of KaHx in cultures overexpressing BECN1 or ATG7. Finally, in vivo inhibition of autophagy by intrastriatal injection of a lentiviral vector expressing a Becn1-targeting shRNA increased the volume of intact striatum in a rat model of severe neonatal cerebral HI. These results clearly show a death-mediating role of autophagy in hypoxic-excitotoxic conditions and suggest that inhibition of autophagy should be considered as a neuroprotective strategy in HI brain injuries.
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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.