Our study demonstrated that stroke-induced C3d+/GFAP+ A1 astrocytes disrupt blood-brain barrier integrity and that blocking C3d+/GFAP+ A1 astrocyte formation using semaglutide attenuates brain injury, suggesting the detrimental role of C3d+/GFAP+ A1 astrocytes in stroke. Here, GFAP is linked to stroke disorder.