Targeting platelet glycoprotein VI attenuates progressive ischemic brain damage before recanalization during middle cerebral artery occlusion in mice

Abstract

In acute ischemic stroke due to large vessel occlusion (LVO) infarcts rapidly grow into the penumbra, which represents dysfunctional, but still viable brain tissue amenable to rescue by vessel recanalization. However, infarct progression and/or delayed patient presentation are serious and frequent limitations of this so far only acute therapy. Thus, a major goal of translational research is to “freeze” the penumbra already during LVO (before opening the vessel) and thereby extend individual time windows for non-futile recanalization. We used the filament occlusion model of the middle cerebral artery (MCAO) in mice and assessed progressive infarction under occlusion at 2, 3, and 4 h after onset. We show that blocking the activatory platelet receptor glycoprotein (GP)VI substantially delayed progressive neocortical infarction compared to isotype control antibody treated mice. Moreover, the local vascular recruitment of infiltrating neutrophils and T-cells was mitigated. In conclusion, our experimental data support ongoing clinical trials blocking platelet GPVI in acute ischemic stroke.