TY - JOUR T1 - Thrombin Activity Associated with Neuronal Damage during Acute Focal Ischemia JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7622 LP - 7631 DO - 10.1523/JNEUROSCI.0369-12.2012 VL - 32 IS - 22 AU - Bo Chen AU - Beth Friedman AU - Michael A. Whitney AU - Jessica A. Van Winkle AU - I-Farn Lei AU - Emilia S. Olson AU - Qun Cheng AU - Benedict Pereira AU - Lifu Zhao AU - Roger Y. Tsien AU - Patrick D. Lyden Y1 - 2012/05/30 UR - http://www.jneurosci.org/content/32/22/7622.abstract N2 - Mechanisms of ischemic neuronal and vascular injury remain obscure. Here we test the hypothesis that thrombin, a blood-borne coagulation factor, contributes to neurovascular injury during acute focal ischemia. Stroke was induced in adult Sprague Dawley rats by occluding the middle cerebral artery. Intra-arterial thrombin infusion during ischemia significantly increased vascular disruption and cellular injury. Intravenous infusion of argatroban, a direct thrombin inhibitor, alleviated neurovascular injury. Immunostaining showed thrombin on neurons in the ischemic core. Using an activatable cell-penetrating peptide engineered to detect thrombin activity, we discovered that thrombin proteolytic activity was specifically associated with neuronal damage during ischemia. Protease activated receptor-1, the presumptive thrombin receptor, appeared to mediate ischemic neurovascular injury. Furthermore, rats receiving thrombin during ischemia showed cognitive deficit, whereas rats receiving argatroban retained intact learning and memory. These results suggest a potential role for thrombin contributing to neurovascular injury and several potential avenues for neuroprotection. ER -