Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes  

作　　者：Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni 

机构地区：[1]Division of Brain Science,Institute of Pediatric Research,Children’s Hospital of Soochow University,Suzhou,Jiangsu Province,China [2]Department of Pediatric Orthopedics,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China

出　　处：《Neural Regeneration Research》2024年第12期2760-2772,共13页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81871024 (to HN),82301957 (to XW),82001382 (to LL),62127810 (to HN);the Natural Science Foundation of Jiangsu Province of China,No.SBK2020040785 (to LL)。

摘　　要：Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关 键 词：brain injury cerebral palsy HYPOXIA hypoxic-ischemic brain injury inflammation NEUROPROTECTION nicotinamide adenine dinucleotide NEONATE nicotinamide adenine dinucleotide PROTEOMICS 

分 类 号：R742[医药卫生—神经病学与精神病学] R722.1[医药卫生—临床医学]