In acute ischemic stroke (AIS), there is an alarming discrepancy between recanalization rates of up to 70% by combined recombinant tissue-type plasminogen activator (rt-PA) therapy and mechanical thrombectomy, and no clinical benefit in at least every second stroke patient. This is partly due to ischemia/reperfusion (I/R) injury. In a translational approach, we used mice lacking dense- (Unc13d-/-) or α-granules (Nbeal2-/-) and mice after blocking of platelet glycoprotein receptor (GP) Ib conferring protection from I/R injury. These mice underwent transient middle cerebral artery occlusion (tMCAO) and, as in the clinic, were treated with rt-PA. Our data show that rt-PA treatment is still safe in conjunction with selected anti-platelet therapies and pave the way for eagerly awaited additive treatment options in acute human stroke.
Keywords: Glycoprotein receptor Ib; Intracranial bleeding; Ischemic stroke; Platelet secretory activity; Recombinant tissue-type plasminogen activator; Transient middle cerebral artery occlusion.