ArticleExperimental neurology2015
G-CSF attenuates neuroinflammation and stabilizes the blood-brain barrier via the PI3K/Akt/GSK-3β signaling pathway following neonatal hypoxia-ischemia in rats.
Article in Experimental neurology, 2015. 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 It has been retracted, and should not be counted.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 54 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.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 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
- Inhibition of Neuroinflammation by Costunolide Attenuates Hypoxic-Ischemic Brain Damage via the PI3K/AKT Pathway in Neonatal Rats.Molecular neurobiology · 2025Article
- Effect of granulocyte colony-stimulating factor (G-CSF) in functional outcome of acute spinal cord injury patients: A single-blinded randomized controlled trial.Journal of orthopaedics · 2025Article
- Endothelial Neurogranin Regulates Blood-Brain Barrier Permeability via Modulation of the AKT Pathway.Molecular neurobiology · 2025Article
- Inter-alpha Inhibitor Proteins Modulate Microvascular Endothelial Components and Cytokines After Exposure to Hypoxia-Ischemia in Neonatal Rats.Molecular neurobiology · 2025Article
- β-estradiol alleviates hypoxic-ischemic brain damage in neonatal rats through the GPER1-mediated AKT/NF-κB signaling pathway.Archives of medical science : AMS · 2025Article
- Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives.Molecular neurobiology · 2024Review
- Targeting the Multiple Complex Processes of Hypoxia-Ischemia to Achieve Neuroprotection.International journal of molecular sciences · 2024Review
- Dynamics simulations of hypoxia inducible factor-1 regulatory network in cancer using formal verification techniques.Frontiers in molecular biosciences · 2024Article
- Arsenic and Tau Phosphorylation: a Mechanistic Review.Biological trace element research · 2023Review
- Monocytes in neonatal stroke and hypoxic-ischemic encephalopathy: Pathophysiological mechanisms and therapeutic possibilities.Neuroprotection (Chichester, England) · 2023Review
- Abnormal DNA methylation analysis of leucine-rich glioma-inactivated 1 antibody encephalitis reveals novel methylation-driven genes related to prognostic and clinical features.Clinical epigenetics · 2023Article
- Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.BMC oral health · 2023Article
- The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.Nature communications · 2023Article
- Cytokine profiles in intensive care unit delirium.Acute and critical care · 2022Article
- Granulocyte colony-stimulating factor protected against brain injury in a rat cerebral hemorrhage model by modulating inflammation.Experimental animals · 2022Article
- Neuroprotective Mechanism of Icariin on Hypoxic Ischemic Brain Damage in Neonatal Mice.Oxidative medicine and cellular longevity · 2022Article
- Long Non Coding RNA Based Regulation of Cerebrovascular Endothelium.Frontiers in genetics · 2022Review
- Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies.Frontiers in immunology · 2022Review
- Effects of intranasal guanosine administration on brain function in a rat model of ischemic stroke.Purinergic signalling · 2021Article
Corrections and comments
- Expression of concern
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveNeonatal hypoxia occurs in approximately 60% of premature births and is associated with a multitude of neurological disorders. While various treatments have been developed, translating them from bench to bedside has been limited. We previously showed G-CSF administration was neuroprotective in a neonatal hypoxia-ischemia rat pup model, leading us to hypothesize that G-CSF inactivation of GSK-3β via the PI3K/Akt pathway may attenuate neuroinflammation and stabilize the blood-brain barrier (BBB).
methodsP10 Sprague-Dawley rat pups were subjected to unilateral carotid artery ligation followed by hypoxia for 2.5h. We assessed inflammation by measuring expression levels of IKKβ, NF-κB, TNF-α, IL-1β, IL-10, and IL-12 as well as neutrophil infiltration. BBB stabilization was evaluated by measuring Evans blue extravasation, and Western blot analysis of Claudin-3, Claudin-5, ICAM-1, and VCAM-1. MEASUREMENTS AND MAIN
resultsFirst, the time course study showed that p-β-catenin/β-catenin, IKKβ, and NF-κB expression levels peaked at 48h post-HI. The knockdown of GSK-3β with siRNA prevented the HI-induced increase of p-β-catenin/β-catenin, IKKβ, and NF-κB expression levels 48h after HI. G-CSF treatment reduced brain water content and neuroinflammation by downregulating IKKβ, NF-κB, TNF-α, IL-1β, and IL-12 and upregulating IL-10, thereby reducing neutrophil infiltration. Additionally, G-CSF stabilizes the BBB by downregulating VCAM-1 and ICAM-1, as well as upregulating Claudins 3 and 5 in endothelial cells. G-CSFR knockdown by siRNA and Akt inhibition by Wortmannin reversed G-CSF's neuroprotective effects.
conclusionsWe demonstrate G-CSF plays a pivotal role in attenuating neuroinflammation and BBB disruption following HI by inactivating GSK-3β through the PI3K/Akt pathway.
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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.