ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02551081 (Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units), which is not on this map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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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
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.
Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Neurological Outcome Following Newborn Encephalopathy With and Without Perinatal Infection: A Systematic Review.Frontiers in pediatrics · 2021Pooled it
- The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?Journal of neuroinflammation · 2026Review
- Association of monocyte to lymphocyte ratio with length of stay in intensive care unit in neonatal apnea modified by treatment.Translational pediatrics · 2025Article
- The Immunomodulatory Role of Regulatory T Cells in Preterm Birth and Associated Pregnancy Outcomes.International journal of molecular sciences · 2024Review
- Brain Maturation as a Fundamental Factor in Immune-Neurovascular Interactions in Stroke.Translational stroke research · 2024Review
- Article
- Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury.Neural regeneration research · 2023Article
- No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study.Frontiers in pediatrics · 2023Article
- Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia.Neurobiology of disease · 2022Article
- Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder.Journal of autism and developmental disorders · 2022Article
- Azithromycin reduces inflammation-amplified hypoxic-ischemic brain injury in neonatal rats.Pediatric research · 2022Article
- Monocytes promote acute neuroinflammation and become pathological microglia in neonatal hypoxic-ischemic brain injury.Theranostics · 2022Article
- Peripheral immune cells and perinatal brain injury: a double-edged sword?Pediatric research · 2022Review
- The role of lymphocytes in neonatal encephalopathy.Brain, behavior, & immunity - health · 2021Review
- Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis.JCI insight · 2021Article
- Microglia-leucocyte axis in cerebral ischaemia and inflammation in the developing brain.Acta physiologica (Oxford, England) · 2021Review
- The emerging role of FTY720 as a sphingosine 1-phosphate analog for the treatment of ischemic stroke: The cellular and molecular mechanisms.Brain and behavior · 2021Review
- FTY720 Modulates Microglia Toward Anti-inflammatory Phenotype by Suppressing Autophagy via STAT1 Pathway.Cellular and molecular neurobiology · 2021Article
- Necrotizing enterocolitis induces T lymphocyte-mediated injury in the developing mammalian brain.Science translational medicine · 2021Article
- Current Therapies for Neonatal Hypoxic-Ischaemic and Infection-Sensitised Hypoxic-Ischaemic Brain Damage.Frontiers in synaptic neuroscience · 2021Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
Abstract
Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.
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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.