ArticleGastroenterology2021
Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Role of meningeal lymphatic vessels in brain homeostasis.Frontiers in immunology · 2025Pooled it
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Novel Therapeutic Insights Into Alzheimer's Disease: Glymphatic System and Meningeal Lymphatic Vessels.Aging cell · 2026Review
- The role of ammonia in chronic liver disease.Hepatology communications · 2026Review
- Article
- Association of glymphatic function with 40-Hz neural oscillations, systemic metabolic markers, and cognitive performance in healthy aging adults: An EEG and MRI study.Translational psychiatry · 2026Article
- Virus-like particle vaccine targeting meningeal lymphatic vessels via intradural delivery activates anti-glioma immunity.Journal of neuro-oncology · 2026Article
- Myasthenia Gravis patients have reduced DTI-ALPS-Index and gBOLD-CSF coupling, suggesting impaired brain waste clearance.Brain imaging and behavior · 2026Article
- Central Administration of Recombinant IGF1 Is Neuroprotective in a Rodent Model of Acute Liver Failure.International journal of molecular sciences · 2026Article
- Impact of early glymphatic disorders on the development of vascular dementia.BMC medical imaging · 2026Article
- Neurolymphatic clearance in neurodegenerative disease: Emerging mechanisms and potential translational strategies.JPRAS open · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Identification and validation of circadian rhythm and astrocyte-associated diagnostic and therapeutic model for cirrhosis encephalopathy patients via integrative bioinformatic pipelines andFrontiers in neuroscience · 2026Article
- Beyond AQP-4: convergent glymphatic-meningeal lymphatic dysfunction underlying multifactorial migraine pathogenesis.Frontiers in immunology · 2026Review
- Glymphatic System Alterations in Lung Cancer Patients with Chemotherapy-Related Cognitive ImpairmentCurrent medical imaging · 2026Article
- Glymphatic-meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders.Frontiers in immunology · 2026Review
- Meningeal lymphatics as a therapeutic target for neurodegenerative disorders.Translational neurodegeneration · 2025Review
- 1275-nm Photobiomodulation Alleviates Brain Drainage Impairment as a Promising Therapeutic Strategy for Aging-Related Neurological Decline.Aging cell · 2025Article
- The brain washing system in sepsis-associated encephalopathy.Journal of neuroinflammation · 2025Review
- Emerging Roles of Meningeal Lymphatic Vessels in Ischemic Stroke.Molecular neurobiology · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsHepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE.
methodsA 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis.
resultsCirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1β, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1β) (n = 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P = .035) and tracer dye uptake in the anterior and middle regions of the cortex (P = .006 and .003, respectively), their corresponding meninges (P = .086 and .006, respectively), and the draining lymph nodes (P = .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P = .024).
conclusionsPromoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.
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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.