Background & Aims: Hepatic 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.
Methods: A 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.
Results: Cirrhotic 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).
Conclusions: Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956141 | PMC |
| http://dx.doi.org/10.1053/j.gastro.2020.11.036 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Breaking boundaries: role of the brain barriers in metastatic process.
Fluids Barriers CNS
January 2025
Department of Anatomy, Cellular and Molecular Neurobiology Research Group, Faculty of Medicine, Masaryk University, 625 00, Brno, Czech Republic.
Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently.
View Article and Find Full Text PDFShift work schedules alter immune cell regulation and accelerate cognitive impairment during aging.
J Neuroinflammation
January 2025
Department of Neuroscience and Experimental Therapeutics, School of Medicine, Texas A&M Health Science Center, Bryan, TX, 77807-3260, USA.
Background: Disturbances of the sleep-wake cycle and other circadian rhythms typically precede the age-related deficits in learning and memory, suggesting that these alterations in circadian timekeeping may contribute to the progressive cognitive decline during aging. The present study examined the role of immune cell activation and inflammation in the link between circadian rhythm dysregulation and cognitive impairment in aging.
Methods: C57Bl/6J mice were exposed to shifted light-dark (LD) cycles (12 h advance/5d) during early adulthood (from ≈ 4-6mo) or continuously to a "fixed" LD12:12 schedule.
A universal live vaccine platform against multiple serotypes Streptococcus suis based on polyvalent antigen protein.
Vaccine
January 2025
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University (JIRLAAPS), Yangzhou, China. Electronic address:
Streptococcus suis (S. suis) is a major pathogen that poses a long-term threat to swine populations. Due to its foodborne transmission, this pathogen has recently emerged as a leading cause of meningitis in humans, presenting a significant public health challenge.
View Article and Find Full Text PDFRevolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders.
Int J Mol Sci
December 2024
Department of Anatomy, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Neuroimmunology is reshaping the understanding of the central nervous system (CNS), revealing it as an active immune organ rather than an isolated structure. This review delves into the unprecedented discoveries transforming the field, including the emerging roles of microglia, astrocytes, and the blood-brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual roles in both repair and disease progression, we uncover how these elements contribute to the intricate pathophysiology of neurodegenerative diseases, cerebrovascular conditions, and CNS tumors.
View Article and Find Full Text PDFPhysiological Mechanisms Underlying the Primary Respiratory Mechanism (PRM) and Cranial Rhythmic Impulse (CRI) in Osteopathy: A Systematic Review.
Healthcare (Basel)
December 2024
Faculté des Sciences, CRPN UMR 7077-Aix Marseille Université, Campus St Charles, CNRS-3, Place Victor-Hugo, F-13331 Marseille Cedex 3, France.
Background: Cranial Rhythmic Impulse (CRI) or Primary Respiratory Mechanism (PRM), movement felt on the scalp or the rest of the body, respectively, is a fundamental concept used by osteopaths in their practice for their diagnosis and treatment. However, the physiological basis of this phenomenon remains unclear. Sutherland, the founder of cranial osteopathy, proposed in 1939 that PRM was due to the movement of the cranial bones pulled by the meninges, themselves pushed by the fluctuation of cerebrospinal fluid and the motility of the central nervous system.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!