Although the effector pathways of these complex T-cell and neutrophil responses in AIS await further elucidation, there is accumulating evidence that platelets guide this inflammation by engagement of GPIb and GPVI receptors and granule release (including HMGB1) beyond thrombus formation in experimental and clinical stroke which provides novel therapeutic perspectives (see below) (Fig. 1A,B). Here, HMGB1 is linked to stroke disorder.