ArticleCNS neuroscience & therapeutics2017
Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in-coordination in rats with hepatic encephalopathy.
Article in CNS neuroscience & therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Sildenafil reduced neuroinflammation and improved white matter injury in a rat model of term neonatal hypoxic-ischemic encephalopathy.Scientific reports · 2025Article
- Neurotoxic effects of acyclovir: impacts on oxidative stress, inflammation, and neurotransmitter dynamics in male Wistar rats.Metabolic brain disease · 2025Article
- Blood-brain barrier dysfunction in hepatic encephalopathy: pathophysiology, diagnostic assessment and therapeutic perspectives.Metabolic brain disease · 2025Review
- Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease.Frontiers in immunology · 2025Article
- The Role of Neuroinflammation in the Pathogenesis of Hepatic Encephalopathy.Journal of immunology research · 2025Review
- Infection, inflammation and hepatic encephalopathy from a clinical perspective.Metabolic brain disease · 2024Review
- The Neuroimmune System and the Cerebellum.Cerebellum (London, England) · 2024Review
- Role of peripheral inflammation in minimal hepatic encephalopathy.Metabolic brain disease · 2024Review
- Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Preface for the Vicente Felipo Honorary Issue of Neurochemical Research.Neurochemical research · 2024Article
- Two-Month Voluntary Ethanol Consumption Promotes Mild Neuroinflammation in the Cerebellum but Not in the Prefrontal Cortex, Hippocampus, or Striatum of Mice.International journal of molecular sciences · 2024Article
- Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Golexanolone reduces glial activation in the striatum and improves non-motor and some motor alterations in a rat model of Parkinson's disease.Frontiers in aging neuroscience · 2024Article
- Anti-inflammatory strategies for hepatic encephalopathy: preclinical studies.Arquivos de neuro-psiquiatria · 2023Review
- Golexanolone, a GABACNS neuroscience & therapeutics · 2022Article
- The Interplay between cGMP and Calcium Signaling in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Hyperammonemia Enhances GABAergic Neurotransmission in Hippocampus: Underlying Mechanisms and Modulation by Extracellular cGMP.Molecular neurobiology · 2022Article
- Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation.Biomedicines · 2022Article
- Extracellular Vesicles From Hyperammonemic Rats Induce Neuroinflammation in Cerebellum of Normal Rats: Role of Increased TNFα Content.Frontiers in immunology · 2022Article
- The Role of Sildenafil in Treating Brain Injuries in Adults and Neonates.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPatients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in-coordination. Rats with HE due to portacaval shunts (PCS) show motor in-coordination. We hypothesized that in PCS rats: (i) Motor in-coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone would be due to neuroinflammation; (iii) increasing cGMP would reduce neuroinflammation and GABAergic tone and restore motor coordination. To assess these hypotheses, we assessed if (i) treatment with sildenafil reduces neuroinflammation; (ii) reduced neuroinflammation is associated with reduced GABAergic tone and restored motor coordination.
methodsRats were treated with sildenafil to increase cGMP. Microglia and astrocytes activation were analyzed by immunohistochemistry, extracellular GABA by microdialysis, and motor coordination in the beam walking.
resultsPCS rats show neuroinflammation in cerebellum, with microglia and astrocytes activation, increased IL-1b and TNF-a and reduced YM-1 and IL-4. Membrane expression of the GABA transporter GAT1 is reduced, while GAT3 is increased. Extracellular GABA and motor in-coordination are increased. Sildenafil treatment eliminates neuroinflammation, microglia and astrocytes activation; changes in membrane expression of GABA transporters; and restores motor coordination.
conclusionsThis study supports an interplay between cGMP-neuroinflammation and GABAergic neurotransmission in impairing motor coordination in PCS rats.
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