Influence of Thrombolysis on the Safety and Efficacy of Blocking Platelet Adhesion or Secretory Activity in Acute Ischemic Stroke in Mice.

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.