Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia
George Zaki Ghali1
Michael George Zaki Ghali2
1.United States Environmental Protection Agency,Arlington,VA,USA;Department of Toxicology,Purdue University,West Lafayette,IN,USA2.Department of Neurological Surgery,University of California San Francisco,San Francisco,CA,USA;Department of Neurobiology and Anatomy,Drexel University College of Medicine,Philadelphia,PA,USA
摘要：Nafamostat mesylate, an apparent soi-disant panacea of sorts, is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass, mitigate the inflammatory response in patients diagnosed with acute pancreatitis, and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East. The serine protease inhibitor na-famostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia. Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases, neuroinflammatory signaling cascades, and the endoplasmic reticulum stress responses, down-regulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents, modulating the activity of intracellular signal transduction pathways, and supporting neuronal survival (brain-derived neurotrophic factor/TrkB/ERK1/2/CREB, nuclear factor kappa B. The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture. Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in pa-tients undergoing cardiac, hepatic, renal, or intestinal transplant, preventing allograft rejection, and treating solid organ malignancies. Neuroprotective effects mediated by nafamostat mesylate support the wise con-duct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.
机标关键词：
论文发表日期：2020-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：18( 2217-2234 )
英文信息