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- W4365517696 endingPage "106669" @default.
- W4365517696 startingPage "106669" @default.
- W4365517696 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." @default.
- W4365517696 created "2023-04-15" @default.
- W4365517696 creator A5002409979 @default.
- W4365517696 creator A5003632020 @default.
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- W4365517696 creator A5089434258 @default.
- W4365517696 date "2023-05-01" @default.
- W4365517696 modified "2023-10-01" @default.
- W4365517696 title "Conditional deletion of LRRC8A in the brain reduces stroke damage independently of swelling-activated glutamate release" @default.
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- W4365517696 doi "https://doi.org/10.1016/j.isci.2023.106669" @default.