Studies the potentiation of Tao-Hong-Si-Wu-Tang and rt-PA in blood clot-induced ischemic stroke and lowering the side effect of subarachidonic hemorrhage

Stroke, a leading cause of mortality and morbidity in the world. Although, our knowledge about the molecular and cellular pathophysiology of brain injury after focal ischemia, the development of new drugs intreating acute ischemia stroke has not progressed rapidly. Chinese medicine has long been considered as therapeutic value for stroke and heart attack. Although western medicine has arisen this view recently. To treat stroke, traditional Chinese medicical practitioners prescribe herbs that could open the blood vessels and promote the blood flow. Tao-Hong-Si-Wu-Tang, a Chinese formula, this dietary supplement used in treating ischemic stroke for a long time. Intravenous recombinant tissue plasminogen activator (rt-PA) remains the only ischemic stroke therapy which is established to improve clinical outcome. However, the use of this thrombolytic agent has been limited due to this deliver treatment within a narrow therapeutic time window, and the excess risk of brain hemorrhage and edema. Hence, it is important to develop strategies that could safely extend the therapeutic time window and limit the risk of brain hemorrhage for rt-PA, it could leads to increase the utilization of this effective treatment. In our previous study, we found that Tao-Hong-Si-Wu-Tang (0.7 g/kg/day) significantly reduced stroke approximately 20% (Evidence-Based Complementary and Alternative Medicine 2011: 9; doi:10.1155/2011/803015). In this project, we further investigate the synergic effect of Tao-Hong-Si-Wu-Tang and rt-PA in rat thromboembolic stroke. In this study, we fix the dose of Tao-Hong-Si-Wu-Tang (0.7 g/kg/day) associated with the reduced and in increased the dose of rt-PA (12, 8, and 4 mg/kg). On the other hand, we also evaluate the side effect of subarachidonic hemorrhage (SAH) in rats induced by the combination of Tao-Hong-Si-Wu-Tang (0.7 g/kg/day) and rt-PA (12, 8, and 4 mg/kg). Hemorrhage is to be quantified with grading system for SAH. The expressions of MMP-9, caspases, HIF-1 alpha, iNOS, TNF-alpha, VEGF, p-Akt, nitrotyrosine and free radical (i.e., OH.) formation in brain tissues will be also assessed. Through this study, we will be understood the synergistic effect of Tao-Hong-Si-Wu-Tang and rt-PA in reducing ischemic stroke and further provide a rational basis of their regulatory mechanisms. The experimental design and results of this study will considerably be relevant in application of traditional Chinese medicine.