ArticleJournal of neuroinflammation2026
Targeting the intestinal TLR4-GABA
Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
2 citing papers in PubMed.
- Gut Microbiota and Ischemic Stroke: From Pre-Stroke Dysbiosis and Acute-Phase Changes to Therapeutic Applications.Brain and behavior · 2026Review
- Gut microbiome-immune-metabolic mechanisms in cerebrovascular disease: evidence-graded insights from cerebral small vessel disease, ischemic stroke, and intracerebral hemorrhage.Frontiers in microbiology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundStroke-induced gut dysbiosis exacerbates brain injury via the toll-like receptor 4 (TLR4) signaling pathway. However, the role of intestinal-specific TLR4 in ischemic stroke remains unclear. This study aimed to investigate the role of intestinal-specific TLR4 in the acute phase of post-stroke recovery and to explore the underlying gut-brain mechanisms.
methodsA murine ischemic stroke model was established, and intestinal-specific interventions were performed using TLR4 inhibitors, agonists, and conditional knockout mice. Post-stroke brain injury, systemic inflammation, and gut barrier function were systematically evaluated. Transcriptomic profiling and 16 S rRNA sequencing were integrated to elucidate the regulatory mechanisms of intestinal TLR4 signaling in stroke outcomes.
resultsPharmacological inhibition of intestinal TLR4 ameliorated, whereas its activation exacerbated, both cerebral and intestinal injury following stroke. Intestinal epithelial-specific TLR4 knockout (TLR4flox/flox; VilCre) significantly reduces cerebral infarction, improves neurological function, alleviates neuronal damage, decreases microglial activation, and preserves intestinal barrier integrity after stroke. Compared to brain-specific TLR4 knockout mice (TLR4flox/flox; Emx1Cre), intestinal epithelial-specific TLR4 knockout mice exhibit greater efficacy in alleviating brain injury, reducing systemic and neuroinflammation and protecting the gut barrier following stroke. RNA sequencing reveals upregulation of gamma-aminobutyric acid type A (GABAA) receptor signaling in the colon of TLR4flox/flox; VilCre mice. The protective effects of intestinal epithelial-specific TLR4 knockout are abolished by GABAA receptor inhibition, highlighting the role of the intestinal TLR4-GABAA axis in stroke recovery. Intestinal epithelial-specific TLR4 knockout reshapes the gut microbiota composition after stroke, and the altered microbial taxa, such as Bacteroides and Prevotella, are closely associated with improved neurological outcomes and upregulation of colonic GABAA receptors.
conclusionThis study identifies intestinal TLR4 as a key determinant of stroke outcomes during the acute phase and establishes the intestinal TLR4-GABAA signaling axis as a central mechanistic pathway mediating gut-brain crosstalk after stroke.
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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.