TLR4 and ischemic stroke: Moreover, in mice with permanent ischemic stroke and in early phase clinical studies, ApTOLL proved superior cerebroprotective activity and better tolerability than TAK-242 (a TLR4 inhibitor), due to its modulatory effects on circulating leukocytes and on local immune reactivity; its accumulation into brain ischemic regions; its reduction effects on the infiltrating neutrophils density; and on edema volume, thus ameliorating neurofunctional disturbances and hemorrhagic risk [126].