Abstract
Hypoxic–ischemic brain injury is an important cause of neonatal neurological deficits. Our previous study demonstrated that dexmedetomidine (Dex) provided neuroprotection against neonatal hypoxic brain injury; however, the underlying mechanisms remain incompletely elucidated. Overactivation of NADPH oxidase 2 (NOX2) can cause neuronal apoptosis and neurological deficits. Hence, we aimed to investigate the role of neuronal NOX2 in Dex-mediated neuroprotection and to explore its potential mechanisms. Hypoxic injury was modeled in neonatal rodents in vivo and in cultured hippocampal neurons in vitro. Our results showed that pre- or post-treatment with Dex improved the neurological deficits and alleviated the hippocampal neuronal damage and apoptosis caused by neonatal hypoxia. In addition, Dex treatment significantly suppressed hypoxia-induced neuronal NOX2 activation; it also reduced oxidative stress, as evidenced by decreases in intracellular reactive oxygen species (ROS) production, malondialdehyde, and 8-hydroxy-2-deoxyguanosine, as well as increases in the antioxidant enzymatic activity of superoxide dismutase and glutathione peroxidase in neonatal rat hippocampi and in hippocampal neurons. Lastly, the posthypoxicneuroprotective action of Dex was almost completely abolished in NOX2-deficient neonatal mice and NOX2-knockdown neurons. In conclusion, our data demonstrated that neuronal NOX2-mediated oxidative stress is involved in the neuroprotection that Dex provides against apoptosis and neurological deficits in neonates following hypoxia.
Funder
National Natural Science Foundation of China
Joint Funds for the Innovation of Science and Technology, Fujian Province
Training Project for Talents of Fujian Provincial Health Commission
Natural Science Foundation of Fujian Province
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Cited by
5 articles.
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