ArticleBrain, behavior, and immunity2021
INT-777 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TGR5/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats.
Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans.Translational stroke research · 2022Pooled it
- Integrated multi-omics and functional analyses reveal a GDCA-TGR5-mediated immunometabolic signature in anorexia nervosa.European archives of psychiatry and clinical neuroscience · 2026Article
- Microbiota-gut-brain axis and bile acids-driven neuromodulation.Neural regeneration research · 2026Article
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- Phosphodiesterase 4 regulates pyroptosis in subarachnoid hemorrhage.Neural regeneration research · 2026Article
- Role of gut microbiota metabolites in maintaining intestinal health and preventing weaning-associated diarrhea in piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Maraviroc Attenuates Neuronal Apoptosis by Inhibiting CCR5-Mediated Microglial Activation After Subarachnoid Hemorrhage.Neurochemical research · 2026Article
- Genistein-3'-sodium sulfonate improves neuroinflammation, blood-brain barrier function, and microglial activation after chronic cerebral hypoperfusion by regulating TGR5.Metabolic brain disease · 2026Article
- Targeting beta-2 adrenergic receptor attenuates schizophrenia-like behavioral effects induced by ketamine in mice: cAMP/PKA/BDNF-PEA-3 and RIM-1α signaling pathways involvement.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Development and validation of programmed cell death related genes in intracranial aneurysms.BMC neurology · 2026Article
- Intrathecal injection of rituximab inhibits microglial M1 polarisation to alleviate neuropsychiatric SLE symptoms via the cAMP/PKA/CREB signalling pathway.Lupus science & medicine · 2026Article
- Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson's disease in an MPTP mouse model.Journal of advanced research · 2026Article
- Cognitive-exercise dual-task training delays natural aging/D-galactose-induced cognitive decline in mice.Cellular & molecular biology letters · 2026Article
- Hesperetin alleviates neuronal pyroptosis by promoting mitophagy via DHCR24/BACE1 signaling pathway after subarachnoid hemorrhage in mice.Apoptosis : an international journal on programmed cell death · 2026Article
- Pathogenesis and intervention strategies for metabolic dysfunction-associated fatty liver disease from the perspective of the gut-microbiota-liver axis.Frontiers in immunology · 2026Review
- The liver-brain axis, from its function to preventive therapeutic strategies in diseases.Frontiers in endocrinology · 2026Review
- Integrated Multi-Omics Analyses Identify Acupuncture-Associated Changes in Gut Microbiota, Short-Chain Fatty Acids, and TNC Gene Expression in Chronic Migraine Rats.Journal of inflammation research · 2026Article
- Bile acid signaling at the gut-vascular interface: a novel modulator of hantavirus endothelial barrier dysfunction.Frontiers in cellular and infection microbiology · 2026Article
- Aerobic Exercise-Induced TGF-β Receptor Reprogramming Disrupts Neutrophil-Microglia Crosstalk to Attenuate Early Brain Injury after Subarachnoid Hemorrhage.Research (Washington, D.C.) · 2026Article
- Gut microbiota and metabolites as potential modulators of cognitive impairment after aneurysmal subarachnoid hemorrhage: a hypothesis-driven review.Frontiers in microbiology · 2026Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundInflammasome-mediated neuroinflammation plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of the TGR5 receptor has been shown to be neuroprotective in a variety of neurological diseases. This study aimed to investigate the effects of the specific synthetic TGR5 agonist, INT-777, in attenuating NLRP3-ASC inflammasome activation and reducing neuroinflammation after SAH.
methodsOne hundred and eighty-four male Sprague Dawley rats were used. SAH was induced by the endovascular perforation. INT-777 was administered intranasally at 1 h after SAH induction. To elucidate the signaling pathway involved in the effect of INT-777 on inflammasome activation during EBI, TGR5 knockout CRISPR and PKA inhibitor H89 were administered intracerebroventricularly and intraperitoneally at 48 h and 1 h before SAH. The SAH grade, short- and long-term neurobehavioral assessments, brain water content, western blot, immunofluorescence staining, and Nissl staining were performed.
resultsThe expressions of endogenous TGR5, p-PKA, and NLRP3-ASC inflammasome were increased after SAH. INT-777 administration significantly decreased NLRP3-ASC inflammasome activation in microglia, reduced brain edema and neuroinflammation, leading to improved short-term neurobehavioral functions at 24 h after SAH. The administration of TGR5 CRISPR or PKA inhibitor (H89) abolished the anti-inflammation effects of INT-777, on NLRP3-ASC inflammasome, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-a), and neutrophil infiltration at 24 h after SAH. Moreover, early administration of INT-777 attenuated neuronal degeneration in hippocampus on 28 d after SAH.
conclusionsINT-777 attenuated NLRP3-ASC inflammasome-dependent neuroinflammation in the EBI after SAH, partially via TGR5/cAMP/PKA signaling pathway. Early administration of INT-777 may serve as a potential therapeutic strategy for EBI management in the setting of SAH.
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