ArticleiScience2023
Conditional deletion of LRRC8A in the brain reduces stroke damage independently of swelling-activated glutamate release.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Subunit-specific roles of LRRC8 proteins in determining glutamate permeability of astrocytic volume-regulated anion channels.American journal of physiology. Cell physiology · 2026Article
- LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy.International journal of molecular sciences · 2026Article
- Astrocytic PYGM attenuates tau pathology by promoting lactate-mediated neuroprotection.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Excitotoxic neuronal death requires superoxide entry into neurons through volume-regulated anion channels.Science advances · 2025Article
- LRRC8 complexes are ATP release channels that regulate platelet activation and arterial thrombosis.Blood · 2025Article
- Astrocytic YAP prevents the glutamate neurotoxicity by upregulation of EAAT2 expression and promotes the gain of stemness in astrocytes in ischemic stroke mice.Cell death & disease · 2025Article
- Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.Molecular neurobiology · 2024Review
- The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.The journal of physiological sciences : JPS · 2024Review
- Mechanobiological insight into brain diseases based on mechanosensitive channels: Common mechanisms and clinical potential.CNS neuroscience & therapeutics · 2024Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The ubiquitous volume-regulated anion channels (VRACs) facilitate cell volume control and contribute to many other physiological processes. Treatment with non-specific VRAC blockers or brain-specific deletion of the essential VRAC subunit LRRC8A is highly protective in rodent models of stroke. Here, we tested the widely accepted idea that the harmful effects of VRACs are mediated by release of the excitatory neurotransmitter glutamate. We produced conditional LRRC8A knockout either exclusively in astrocytes or in the majority of brain cells. Genetically modified mice were subjected to an experimental stroke (middle cerebral artery occlusion). The astrocytic LRRC8A knockout yielded no protection. Conversely, the brain-wide LRRC8A deletion strongly reduced cerebral infarction in both heterozygous (Het) and full KO mice. Yet, despite identical protection, Het mice had full swelling-activated glutamate release, whereas KO animals showed its virtual absence. These findings suggest that LRRC8A contributes to ischemic brain injury via a mechanism other than VRAC-mediated glutamate release.
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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.