ArticleJournal of neuroinflammation2014
TNFR1-JNK signaling is the shared pathway of neuroinflammation and neurovascular damage after LPS-sensitized hypoxic-ischemic injury in the immature brain.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2024Pooled it
- Microstructural white matter abnormalities in pediatric and adult obsessive-compulsive disorder: A systematic review and meta-analysis.Brain and behavior · 2021Pooled it
- Calcium signaling in human and mouse microglia exhibit differential susceptibility to phytocannabinoids.Cell communication and signaling : CCS · 2026Article
- The Role of TNF-α in Neuropathic Pain: An Immunotherapeutic Perspective.Life (Basel, Switzerland) · 2025Review
- Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats.Pediatric research · 2025Article
- Neurotrophomodulatory effect of TNF-α through NF-κB in rat cortical astrocytes.Cytotechnology · 2025Review
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
- Acupuncture Alleviates Chronic Ischemic White Matter Injury in SHR Rats via JNK-NMDAR Circuit.Molecular neurobiology · 2024Article
- Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation.International journal of molecular sciences · 2024Review
- Consequences of oxygen deprivation on myelination and sex-dependent alterations.Molecular and cellular neurosciences · 2023Review
- Heat-killedBioengineering & translational medicine · 2023Article
- Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.Journal of neuroinflammation · 2022Article
- The Effect of TNF-alpha rs1800629 Polymorphism on White Matter Structures and Memory Function in Patients With Schizophrenia: A Pilot Study.Psychiatry investigation · 2022Article
- Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity.Frontiers in physiology · 2022Review
- Enhanced Microglia Activation and Glioma Tumor Progression by Inflammagen Priming in Mice with Tumor Necrosis Factor Receptor Type 2 Deficiency.Life (Basel, Switzerland) · 2021Article
- Patients with obstructive sleep apnea have suppressed levels of soluble cytokine receptors involved in neurodegenerative disease, but normal levels with airways therapy.Sleep & breathing = Schlaf & Atmung · 2021Article
- Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease.Mediators of inflammation · 2021Review
- Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights.Frontiers in oncology · 2021Review
- Sirtuin 1-dependent regulation of high mobility box 1 in hypoxia-reoxygenated brain microvascular endothelial cells: roles in neuronal amyloidogenesis.Cell death & disease · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxic-ischemia (HI) and inflammation are the two major pathogenic mechanisms of brain injury in very preterm infants. The neurovascular unit is the major target of HI injury in the immature brain. Systemic inflammation may worsen HI by up-regulating neuroinflammation and disrupting the blood-brain barrier (BBB). Since neurons and oligodendrocytes, microvascular endothelial cells, and microglia may closely interact with each other, there may be a common signaling pathway leading to neuroinflammation and neurovascular damage after injury in the immature brain. TNF-α is a key pro-inflammatory cytokine that acts through the TNF receptor (TNFR), and c-Jun N-terminal kinases (JNK) are important stress-responsive kinases.
objectiveTo determine if TNFR1-JNK signaling is a shared pathway underlying neuroinflammation and neurovascular injury after lipopolysaccharide (LPS)-sensitized HI in the immature brain.
methodsPostpartum (P) day-5 mice received LPS or normal saline (NS) injection before HI. Immunohistochemistry, immunoblotting and TNFR1- and TNFR2-knockout mouse pups were used to determine neuroinflammation, BBB damage, TNF-α expression, JNK activation, and cell apoptosis. The cellular distribution of p-JNK, TNFR1/TNFR2 and cleaved caspase-3 were examined using immunofluorescent staining.
resultsThe LPS + HI group had significantly greater up-regulation of activated microglia, TNF-α and TNFR1 expression, and increases of BBB disruption and cleaved caspase-3 levels at 24 hours post-insult, and showed more cortical and white matter injury on P17 than the control and NS + HI groups. Cleaved caspase-3 was highly expressed in microvascular endothelial cells, neurons, and oligodendroglial precursor cells. LPS-sensitized HI also induced JNK activation and up-regulation of TNFR1 but not TNFR2 expression in the microglia, endothelial cells, neurons, and oligodendrocyte progenitors, and most of the TNFR1-positive cells co-expressed p-JNK. Etanercept (a TNF-α inhibitor) and AS601245 (a JNK inhibitor) protected against LPS-sensitized HI brain injury. The TNFR1-knockout but not TNFR2-knockout pups had significant reduction in JNK activation, attenuation of microglial activation, BBB breakdown and cleaved caspase-3 expression, and showed markedly less cortical and white matter injury than the wild-type pups after LPS-sensitized HI.
conclusionTNFR1-JNK signaling is the shared pathway leading to neuroinflammation and neurovascular damage after LPS-sensitized HI in the immature brain.
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.