摘要
Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.
Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.
基金
supported by grants from the National Natural Science Foundation of China(81200939 and31260242)
National Science and Technology Supporting Plan of China(2014BAI01B00)
Natural Science Foundation of Yunnan Province,China(2011FB060)
the National Undergraduate Innovation Fund of China(201310678001)
the Undergraduate Innovation Fund of Yunnan Province,China(6011202105)
Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University for his support throughout the study
