ArticleNeurobiology of disease2016
Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Intranasal therapies for neonatal hypoxic-ischemic encephalopathy.Neural regeneration research · 2026Article
- Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.CNS neuroscience & therapeutics · 2026Article
- A Novel Therapeutic Target for Pediatric Pneumonia: Sestrin2.Medicina (Kaunas, Lithuania) · 2025Article
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Activation of Src Kinase Mediates the Disruption of Adherens Junction in the Blood-labyrinth Barrier after Acoustic Trauma.Current neurovascular research · 2024Article
- Glucose promotes cell growth and casein synthesis via ATF4/Nrf2-Sestrin2- AMPK-mTORC1 pathway in dairy cow mammary epithelial cells.Animal biotechnology · 2023Article
- Significance of serum sestrin2 as a biomarker of severity and functional outcome in acute intracerebral hemorrhage: a prospective observational longitudinal study.BMC neurology · 2023Observational
- Association between the antioxidant properties of SESN proteins and anti-cancer therapies.Amino acids · 2023Review
- Sestrin2 as a Protective Shield against Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases.Cell death & disease · 2023Review
- Endurance training and MitoQ supplementation improve spatial memory, VEGF expression, and neurogenic factors in hippocampal tissue of rats.Journal of clinical and translational research · 2023Article
- Sestrin2 protects against hypoxic nerve injury by regulating mitophagy through SESN2/AMPK pathway.Frontiers in molecular biosciences · 2023Article
- Serum Sestrin2 Emerges as a Prognostic Biomarker of Human Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Cohort Single-Center Study.International journal of general medicine · 2023Article
- Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice.International journal of molecular sciences · 2022Article
- Physapruin A Induces Reactive Oxygen Species to Trigger Cytoprotective Autophagy of Breast Cancer Cells.Antioxidants (Basel, Switzerland) · 2022Article
- VEGF, a Key Factor for Blood Brain Barrier Injury After Cerebral Ischemic Stroke.Aging and disease · 2022Article
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
- The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases.Cell & bioscience · 2022Review
- Sestrin2 induction contributes to anti-inflammatory responses and cell survival by globular adiponectin in macrophages.Archives of pharmacal research · 2022Article
- Sestrin2 in hypoxia and hypoxia-related diseases.Redox report : communications in free radical research · 2021Review
Corrections and comments
- Expression of concern
- Retracted
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveHypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries.
methodsRat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability.
resultsRats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability.
conclusionsrh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury.
Indexed as
Identifiers
What OpenQuestion holds
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.