The SWELL1 channel in astrocytes has been proposed to be involved in ischemic stroke by releasing glutamate.[32] We previously generated astrocyte‐specific Swell1 knockout (GFAP‐cKO) mice and found that Swell1 deletion in astrocytes significantly reduces brain infarcts and improves neurological outcomes after experimental stroke.[21] To determine its underlying neuroprotective mechanism and the extent to which astrocytes employ the SWELL1 channel to release glutamate in ischemic stroke, we performed tMCAO surgery in WT mice and prepared acute brain slices after ischemia. This evidence concerns the gene LRRC8A and ischemic stroke.