Molecular Pharmacology and Pathology of Strokes PDF

Stroke, an important neurological disease, is becoming an increasingly non-communicable ailment and is the second leading cause of death after coronary heart disease in developed countries [1]. Present treatment options for stroke are adapting lifestyle practice, diabetes treatment, drugs, and other factors management, but no cure is yet available, despite new insights into the molecular and therapeutic targets. Discoveries in explicating the molecular pharmacology in cerebrovascular function and thrombosis have led to significant advancements in the current treatment paradigm for patients with stroke. Hence, this Special Issue invited scientific papers and reviews from researchers to provide solid evidence from a molecular point of view to scrutinize the molecular pharmacology and pathology of strokes. Platelet activation plays a major role in cardio and cerebrovascular diseases. Platelets also play a key role in the hemostatic process and are associated with various pathological events, such as arterial thrombosis and atherosclerosis.

While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have moved their attention to the synthesis of various ruthenium (Ru) and iridium (Ir) complexes due to their prospective therapeutic values. In this Special Issue, the authors Hsia et al. [2] found that Ir (III)-derived complex, (Ir-11), showed potent antiplatelet activity by inhibiting platelet activation through the suppression of the phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC) cascade and the subsequent suppression of Akt and mitogen-activated protein kinases (MAPKs) activation, ultimately inhibiting platelet aggregation. A detailed in vitro antiplatelet, in vivo antithrombotic and structure-activity relationship (SAR) study was performed on newly synthesized Ir complexes, Ir-1, Ir-2 and Ir-4, in agonists-induced human platelets [3]. This study found that Ir-1 expressively suppressed collagen-induced Akt, PKC, p38MAPKs and JNK phosphorylation. Interestingly, platelet function analyzer (PFA-100) showed that Ir-1 caused a significant increase in collagen-adenosine diphosphate (C-ADP) induced closure times in mice, but Ir-2 and 4 had no effect on these reactions. Moreover, Ir-1 significantly prolonged the platelet plug formation, increased tail bleeding times and reduced the mortality of adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism in mice. Ir-1 has no substitution on its phenyl group; a water molecule (like cisplatin) can replace its chloride ion and, hence, the rate of hydrolysis might be tuned by the substituent on the ligand system. These features might have played a role for the observed effects of Ir-1. These results indicate that Ir compounds may be a lead compound to design new antiplatelet drugs for the treatment of thromboembolic diseases.