These data suggested that RIP1K activity is an important contributing factor for astrocyte dysfunction and reactive astrogliosis, and targeting RIP1K presents a better strategy in maintaining normal astrocytic function and suppressing the VEGF-D/VEGFR-3 signaling pathways in astrocytes, leading to blocking the excessive reactive astrogliosis and improving brain function after ischemic stroke. Here, VEGFD is linked to ischemic stroke.