Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia  

作　　者：George Zaki Ghali Michael George Zaki Ghali 

机构地区：[1]United States Environmental Protection Agency,Arlington,VA,USA [2]Department of Toxicology,Purdue University,West Lafayette,IN,USA [3]Department of Neurological Surgery,University of California San Francisco,San Francisco,CA,USA [4]Department of Neurobiology and Anatomy,Drexel University College of Medicine,Philadelphia,PA,USA

出　　处：《Neural Regeneration Research》2020年第12期2217-2234,共18页中国神经再生研究（英文版）

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 nafamostat 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,downregulating 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 patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.

关 键 词：apoptosis cerebrovascular EXCITOTOXICITY infarction ISCHEMIA nafamostat mesylate necrosis neuroprotection serine protesae subarachnoid hemorrhage 

分 类 号：R743.3[医药卫生—神经病学与精神病学]