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

• Published in: Neural regeneration research Vol. 19; no. 12; pp. 2760 - 2772
• Main Authors: Xu, Xiaowen, Wang, Xinxin, Zhang, Li, Jin, Yiming, Li, Lili, Jin, Meifang, Li, Lianyong, Ni, Hong
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer - Medknow 01.12.2024; Medknow Publications & Media Pvt. Ltd; Division of Brain Science,Institute of Pediatric Research,Children's Hospital of Soochow University,Suzhou,Jiangsu Province,China%Department of Pediatric Orthopedics,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China; Wolters Kluwer Medknow Publications
• Edition: 2
• Subjects: brain injury; cerebral palsy; hypoxia; hypoxic-ischemic brain injury; inflammation; neuroprotection; nicotinamide adenine dinucleotide; neonate; nicotinamide adenine dinucleotide; proteomics; Hypoxia; Ischemia; Kinases; Proteins; Proteomics; Research Article; Traumatic brain injury; nicotinamide adenine dinucleotide; hypoxia; brain injury; proteomics; inflammation; neuroprotection; cerebral palsy; neonate; hypoxic-ischemic brain injury
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/NRR.NRR-D-23-01490

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 before 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.