ArticleCNS neuroscience & therapeutics2015
NF-κB Signaling is Involved in the Effects of Intranasally Engrafted Human Neural Stem Cells on Neurofunctional Improvements in Neonatal Rat Hypoxic-Ischemic Encephalopathy.
Article in CNS neuroscience & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 5 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 5 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.Molecular neurobiology · 2025Pooled it
- Stem cell-based interventions for the treatment of stroke in newborn infants.The Cochrane database of systematic reviews · 2023Pooled it
- Neural stem cell treatment for perinatal brain injury: A systematic review and meta-analysis of preclinical studies.Stem cells translational medicine · 2021Pooled it
- Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.The Cochrane database of systematic reviews · 2020Pooled it
- Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants.The Cochrane database of systematic reviews · 2019Pooled it
- Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial.Stem cell research & therapy · 2023Trial
- Intranasal therapies for neonatal hypoxic-ischemic encephalopathy.Neural regeneration research · 2026Article
- Neuroprotective and Immunomodulatory effects of human hair follicle stem cells on streptozotocin-induced memory impairment in rats: insights into inflammation and neurotrophic mechanisms.Molecular biology reports · 2025Article
- Inhibition of Neuroinflammation by Costunolide Attenuates Hypoxic-Ischemic Brain Damage via the PI3K/AKT Pathway in Neonatal Rats.Molecular neurobiology · 2025Article
- An optimized method for directed differentiation of hypothalamic neural stem cells in a 3D culture system.Scientific reports · 2025Article
- Human Neural Stem Cells Reduce Hypoxia-Ischemic Neurological Impairment Through the Regulation of Inflammatory M1/M2 Microglias in Rats.Neuropsychiatric disease and treatment · 2025Article
- Pharmacological Strategies and Surgical Management of Posthemorrhagic Hydrocephalus Following Germinal Matrix-Intraventricular Hemorrhage in Preterm Infants.Current neuropharmacology · 2025Review
- Diabetes drugs activate neuroprotective pathways in models of neonatal hypoxic-ischemic encephalopathy.EMBO molecular medicine · 2024Article
- Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.Open life sciences · 2024Article
- Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies: a systematic analysis of therapeutic efficacy and study design.Neuroprotection (Chichester, England) · 2023Article
- Neuroprotection of NSC Therapy is Superior to Glibenclamide in Cardiac Arrest-Induced Brain Injury via Neuroinflammation Regulation.Translational stroke research · 2023Article
- A Tale of Two: When Neural Stem Cells Encounter Hypoxia.Cellular and molecular neurobiology · 2023Review
- Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants.The Cochrane database of systematic reviews · 2023Review
- Lasting mesothalamic dopamine imbalance and altered exploratory behavior in rats after a mild neonatal hypoxic event.Frontiers in integrative neuroscience · 2023Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimHypoxic-ischemic encephalopathy (HIE) is a common neurological disease in infants with persistent neurobehavioral impairments. Studies found that neural stem cell (NSC) therapy benefits HIE rats; however, the mechanisms underlying are still unclear. The current study investigated the efficacy and molecular events of human embryonic neural stem cells (hNSCs) in neonatal hypoxic-ischemic (HI) rats.
methodsPKH-26-labeled hNSCs were intranasally delivered to P7 Sprague Dawley rats 24 h after HI. Neurobehavioral tests were performed at the indicated time after delivery: righting reflex and gait testing at D1, 3, 5, and 7; grid walking at D7 and 14; social choice test (SCT) at D28; and Morris water maze from D35 to 40. Protein expression was determined by Western blot analysis. Brain damage was assessed by cresyl violet staining and MBP staining. hNSC distribution and differentiation were observed by in vivo bioluminescence imaging and immunofluorescence staining.
results(1) hNSCs migrated extensively into brain areas within 24 h after the delivery, survived even at D42 with the majority in ipsi-hemisphere, and could be co-labeled with NeuN or GFAP. (2) hNSCs reduced the upregulation in cytosolic IL-1β, p-IκBα, and NF-κB p65 levels, whereas enhanced nuclear p65 expression in HI rats at D3 after the delivery. (3) hNSCs decreased HI-induced brain tissue loss and white matter injury at D42 after the delivery. (4) hNSCs improved neurological outcomes in HI rats in the tests of righting reflex (within 3 days), gait (D5), grid (D7), SCT (D28), and water maze (D42).
conclusionIntranasal delivery of hNSCs could prevent HI-induced brain injury and improve neurobehavioral outcomes in neonatal HI rats, which is possibly related to the modulation of NF-κB signaling.
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