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The effect of Cathepsin S (CatS), a kind of microglial lysosomal cysteine protease, on brain ischemia remains unclear.Here we investigated the effect of CatS deficiency on ischemic brain damage in male mice which were subjected to intraluminal 90-minutes transient middle cerebral artery occlusion (tMCAO) followed by 24 h or 7 d reperfusion.