ArticleFrontiers in pharmacology2019
Bicuculline Reduces Neuroinflammation in Hippocampus and Improves Spatial Learning and Anxiety in Hyperammonemic Rats. Role of Glutamate Receptors.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Early-life GABA-A receptor blockade with bicuculline attenuates anxiety-like behaviors and cognitive deficits induced by 24-hr sleep deprivation in adult male rats.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Extracellular vesicles from plasma of patients with minimal hepatic encephalopathy induce neuroinflammation and cognitive impairment in rats, which are prevented by treating the patients with rifaximin.Journal of neuroinflammation · 2026Article
- Bicuculline fromComputational and structural biotechnology journal · 2026Article
- Golexanolone Attenuates Neuroinflammation, Fatigue, and Cognitive and Motor Impairment in Diverse Neuroinflammatory Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Effects of Ionotropic GABA Receptor Blockage on the Brain in Rats with Induced Sepsis.Molecular neurobiology · 2025Article
- Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease.Frontiers in immunology · 2025Article
- Extracellular vesicles from mesenchymal stem cells improve neuroinflammation and neurotransmission in hippocampus and cognitive impairment in rats with mild liver damage and minimal hepatic encephalopathy.Stem cell research & therapy · 2024Article
- Infection, inflammation and hepatic encephalopathy from a clinical perspective.Metabolic brain disease · 2024Review
- Role of peripheral inflammation in minimal hepatic encephalopathy.Metabolic brain disease · 2024Review
- Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk.International journal of molecular sciences · 2024Review
- Preface for the Vicente Felipo Honorary Issue of Neurochemical Research.Neurochemical research · 2024Article
- 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
- Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Enhanced Activation of the S1PR2-IL-1β-Src-BDNF-TrkB Pathway Mediates Neuroinflammation in the Hippocampus and Cognitive Impairment in Hyperammonemic Rats.International journal of molecular sciences · 2023Article
- Anti-inflammatory strategies for hepatic encephalopathy: preclinical studies.Arquivos de neuro-psiquiatria · 2023Review
- Article
- Extracellular vesicles from mesenchymal stem cells reduce neuroinflammation in hippocampus and restore cognitive function in hyperammonemic rats.Journal of neuroinflammation · 2023Article
- Golexanolone, a GABACNS neuroscience & therapeutics · 2022Article
- Hyperammonemia Enhances GABAergic Neurotransmission in Hippocampus: Underlying Mechanisms and Modulation by Extracellular cGMP.Molecular neurobiology · 2022Article
- Astrocytes: GABAceptive and GABAergic Cells in the Brain.Frontiers in cellular neuroscience · 2022Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) with mild cognitive impairment. Hyperammonemia is a main contributor to cognitive impairment in MHE, which is mediated by neuroinflammation. GABAergic neurotransmission is altered in hyperammonemic rats. We hypothesized that, in hyperammonemic rats, (a) enhanced GABAergic tone would contribute to induce neuroinflammation, which would be improved by reducing GABAergic tone by chronic bicuculline treatment; (b) this would improve spatial learning and memory impairment; and (c) modulation of glutamatergic neurotransmission would mediate this cognitive improvement. The aim of this work was to assess the above hypotheses. Bicuculline was administrated intraperitoneally once a day for 4 weeks to control and hyperammonemic rats. The effects of bicuculline on microglia and astrocyte activation, IL-1β content, on membrane expression of AMPA and NMDA glutamate receptors subunits in the hippocampus and on spatial learning and memory as well as anxiety were assessed. Treatment with bicuculline reduces astrocyte activation and IL-1β but not microglia activation in the hippocampus of hyperammonemic rats. Bicuculline reverses the changes in membrane expression of AMPA receptor subunits GluA1 and GluA2 and of the NR2B (but not NR1 and NR2A) subunit of NMDA receptors. Bicuculline improves spatial learning and working memory and decreases anxiety in hyperammonemic rats. In hyperammonemia, enhanced activation of GABA
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