ArticleScience translational medicine2018
Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 146 citations in OpenAlex.
- [Berberine attenuates necrotizing enterocolitis-associated brain injury via the TLR4/MyD88/NF-κB/NLRP3 pathway].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- Early-life gastrointestinal inflammation and the developing brain: Unravelling the pathways to long-term cognitive dysfunction.World journal of clinical pediatrics · 2026Review
- The gut-brain ConNECtion: exploring the developmental impact of necrotizing enterocolitis on the neonatal brain.Pediatric research · 2026Review
- Necrotizing enterocolitis.Nature reviews. Disease primers · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Beyond the Gut: Necrotizing Enterocolitis as a Gut-Brain Axis Disorder of Neurodevelopment.Biomedicines · 2026Article
- A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis.Nature communications · 2026Article
- Host-directed nanotherapy for the treatment and imaging of tuberculous meningitis.Theranostics · 2026Article
- Neurodevelopmental impairment in infants with necrotizing enterocolitis: a comprehensive review of mechanisms, outcomes, and emerging strategies.World journal of pediatric surgery · 2026Review
- Remote ischemic conditioning in necrotizing enterocolitis: an extended phase I safety study.Pediatric surgery international · 2025Article
- Hyperbaric oxygen therapy alleviates intestinal and brain damage in experimental necrotizing enterocolitis.Medical gas research · 2025Article
- Gut-Brain Axis in Preterm Infants with Surgical Necrotizing Enterocolitis.American journal of perinatology · 2025Review
- Necrotizing Enterocolitis: What's New and What's Next?International journal of molecular sciences · 2025Review
- Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- Fulminant necrotizing enterocolitis: clinical features and a predictive model.BMC pediatrics · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Human breast milk-derived exosomes attenuate lipopolysaccharide-induced activation in microglia.Journal of neuroinflammation · 2025Article
- The human gut microbiota is associated with host lifestyle: a comprehensive narrative review.Frontiers in microbiology · 2025Review
- Article
28 more citing papers are in PubMed but not listed here.
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21 authors at 4 institutions in 2 countries.
Funding
Abstract
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.
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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.