ArticleGlia2017
Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury.
Article in Glia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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Who cites it
81 citing papers in PubMed, 122 citations in OpenAlex.
- Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.Pediatric research · 2022Trial
- From oxidative stress to epigenetic regulation: Molecular mechanisms of preterm brain injury and neuroprotective strategies (Review).Molecular medicine reports · 2026Review
- Prostaglandins: Key players in immunomodulation of the nervous system.Neural regeneration research · 2026Article
- Neurobehavioral Effects of Two Distinct Anti-Inflammatory Drugs in a Two-Week Chronic Stress Model in Zebrafish.Brain sciences · 2026Article
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?Journal of neuroinflammation · 2026Review
- Astrocytes: Unveiling their role in the molecular mechanism of natural antidepressants.Journal of pharmaceutical analysis · 2026Review
- Oxytocin Modulates Microglial IL-17-Linked Inflammatory Pathways Through the IL-6/COX-2.Life (Basel, Switzerland) · 2026Article
- Vascular-associated bacterial burden and neuroinflammatory transcriptional responses observed in models of pneumonic plague.Frontiers in microbiology · 2026Article
- Neonatal Hypoxic-Ischemic Encephalopathy: From the Limitations of Therapeutic Hypothermia to Precision Intervention.Drug design, development and therapy · 2026Review
- Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Post-ischemic modification of neurogenesis and oligodendrogenesis in rodent models.Frontiers in neural circuits · 2026Review
- Sildenafil reduced neuroinflammation and improved white matter injury in a rat model of term neonatal hypoxic-ischemic encephalopathy.Scientific reports · 2025Article
- A systematic scoring system to optimise the testing of neurotherapeutics in models of perinatal brain injury, with an applied case study of human umbilical-cord MSC.Journal of neuroinflammation · 2025Article
- Astrocyte activation persists one year after TBI: a dynamic shift from inflammation to neurodegeneration.Communications biology · 2025Article
- Combined Maternal Immune Activation and Prenatal Intermittent Hypoxic Stress Lead to Developmental Motor Deficits in Rats: a Two-hit Animal Model for Cerebral Palsy Across Different Age Trajectories.Molecular neurobiology · 2025Article
- Molecular components of the FPR2/ALX pathway participate in astrocyte-neuron resolution responses to afford maneb-induced toxicity.Cellular and molecular life sciences : CMLS · 2025Article
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21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro-inflammatory IL-1β to induce cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production in white matter. First, we assessed COX2 expression in human fetal brain and term neonatal brain affected by hypoxic-ischemic encephalopathy (HIE). In the developing human brain, COX2 was expressed in radial glia, microglia, and endothelial cells. In human term neonatal HIE cases with subcortical WMI, COX2 was strongly induced in reactive astrocytes with "A2" reactivity. Next, we show that OPCs express the EP1 receptor for PGE2, and PGE2 acts directly on OPCs to block maturation in vitro. Pharmacologic blockade with EP1-specific inhibitors (ONO-8711, SC-51089), or genetic deficiency of EP1 attenuated effects of PGE2. In an IL-1β-induced model of NWMI, astrocytes also exhibit "A2" reactivity and induce COX2. Furthermore, in vivo inhibition of COX2 with Nimesulide rescues hypomyelination and behavioral impairment. These findings suggest that neonatal white matter astrocytes can develop "A2" reactivity that contributes to OPC maturation arrest in NWMI through induction of COX2-PGE2 signaling, a pathway that can be targeted for neonatal neuroprotection.
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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.