AD-16 Protects Against Hypoxic-Ischemic Brain Injury by Inhibiting Neuroinflammation  

作　　者：Zhihua Huang Zhengwei Luo Andrea Ovcjak Jiangfan Wan Nai-hong Chen Wenhui Hu Hong-Shuo Sun Zhong-Ping Feng 

机构地区：[1]Department of Physiology,Temerty Faculty of Medicine,University of Toronto,Toronto,ON,M5S 1A8,Canada [2]Department of Surgery,Temerty Faculty of Medicine,University of Toronto,Toronto,ON,M5S 1A8,Canada [3]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100050,China [4]Key Laboratory of Molecular Target and Clinical Pharmacology,State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences and the Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou,511436,Guangdong,China [5]Leslie Dan Faculty of Pharmacy,University of Toronto,Toronto,ON,M5S 3M2,Canada

出　　处：《Neuroscience Bulletin》2022年第8期857-870,共14页神经科学通报（英文版）

基　　金：This work was supported by the Canadian Institutes of Health Research(CIHR PJT-153155);ZPF and a Natural Sciences and Engineering Research Council of Canada Discovery Grant(NSERC RGPIN-2016-04574)to HSS.

摘　　要：Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic(HI)insult in the neonatal brain.AD-16 is a novel anti-inflammatory compound,recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators.In this study,we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation(OGD)in vitro and in mice with neonatal HI brain injury in vivo.We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury.Single dose post-treatment with AD-16(1 mg/kg)improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 h.Chronic administration reduced the mortality rate and preserved whole-brain morphology following neonatal HI.The in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.

关 键 词：NEUROINFLAMMATION Neonatal hypoxic-ischemic brain injury NEUROPROTECTION AD-16 

分 类 号：R651.15[医药卫生—外科学]