ArticleNeuron2023
Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage.
Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Ischemic Cerebral Vascular Disease
An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease
An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Adult Encephalitis
An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Intracerebral Hemorrhage
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Association between serum bilirubin levels and carotid atherosclerosis: a systematic review and meta-analysis.Frontiers in endocrinology · 2025Pooled it
- Regulation of G Protein Signaling 14 protects against cerebral ischemic reperfusion injury by inhibiting the TAK1-JNK/p38 signaling pathway.Histology and histopathology · 2026Article
- Identifying ROCK2 as an intervention target for bilirubin encephalopathy.Fundamental research · 2026Article
- Dyslipidemia is a metabolic hallmark of acute pain in sickle cell disease.medRxiv : the preprint server for health sciences · 2026Article
- Bilirubin as a Modulator of WNK1 Protein Signaling: Implications for Neuroinflammatory Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Compromised hepatic bilirubin clearance drives depressive symptoms via regulating microglial engulfment of dendritic spines.Journal of neuroinflammation · 2026Article
- Neuroimmune Regulation by TRPM2 Channels.Cells · 2026Review
- Neuroprotective role of bilirubin in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- The enhancing therapeutic effect of neonatal jaundice byFrontiers in microbiology · 2026Article
- Wuling San ameliorates cerebral ischemia-reperfusion injury via suppression of the TRPM2/NLRP3 pathway.European journal of medical research · 2025Article
- TRPM2: a pivotal player in tumor progression and a promising therapeutic target.Cancer cell international · 2025Review
- Gut microbiota and metabolites drive chronic sickle cell disease pain in mice.Cell host & microbe · 2025Article
- Bilirubin Targeting WNK1 to Alleviate NLRP3-Mediated Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Bilirubin metabolism and its application in disease prevention: mechanisms and research advances.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Exploring the feasibility and clinical impact of ultrasound microvascular flow imaging in detecting brain injury in hyperbilirubinemia neonates.Scientific reports · 2025Article
- Liver function differences in atherosclerotic cardiovascular disease: a multi-ethnic dual-cohort retrospective study.Frontiers in endocrinology · 2025Article
- Association between serum total bilirubin levels and 28-day all-cause mortality after intracerebral hemorrhage.Frontiers in neurology · 2025Article
- Targeting microglia polarization with Chinese herb-derived natural compounds for neuroprotection in ischemic stroke.Frontiers in cell and developmental biology · 2025Review
- Naringenin Protected Against Blood Brain Barrier Breakdown after Ischemic Stroke through GSK-3β/ β-Catenin Pathway.Neurochemical research · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Stroke prognosis is negatively associated with an elevation of serum bilirubin, but how bilirubin worsens outcomes remains mysterious. We report that post-, but not pre-, stroke bilirubin levels among inpatients scale with infarct volume. In mouse models, bilirubin increases neuronal excitability and ischemic infarct, whereas ischemic insults induce the release of endogenous bilirubin, all of which are attenuated by knockout of the TRPM2 channel or its antagonist A23. Independent of canonical TRPM2 intracellular agonists, bilirubin and its metabolic derivatives gate the channel opening, whereas A23 antagonizes it by binding to the same cavity. Knocking in a loss of binding point mutation for bilirubin, TRPM2-D1066A, effectively antagonizes ischemic neurotoxicity in mice. These findings suggest a vicious cycle of stroke injury in which initial ischemic insults trigger the release of endogenous bilirubin from injured cells, which potentially acts as a volume neurotransmitter to activate TRPM2 channels, aggravating Ca
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What OpenQuestion holds
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.