Adverse and protective influences of adenosine on the newborn and embryo: implications for preterm white matter injury and embryo protection.
Adverse and protective influences of adenosine on the newborn and embryo: implications for preterm white matter injury and embryo protection.
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DOI：
10.1203/pdr.0b013e31820efbcf
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发表时间：
2011-04
影响因子：
3.6
通讯作者：
Wendler CC
中科院分区：
文献类型：
--
作者：
Rivkees SA;Wendler CC
很少有信号分子具有像核苷腺苷那样影响发育中的哺乳动物的潜力。腺苷水平随着组织缺氧和炎症而迅速增加。腺苷拮抗剂包括甲基黄嘌呤、咖啡因和茶碱。腺苷的受体有A1、A2a、A2b和A3腺苷受体（AR）。在出生后，A1 AR激活可能通过改变少突胶质细胞（OL）的发育而导致早产儿白色物质损伤。在围产期脑损伤模型中，咖啡因对脑室周围白色物质损伤（PWMI）和缺氧缺血性脑病（HIE）具有神经保护作用。临床研究表明，咖啡因可降低支气管肺发育不良和脑瘫的发生率，这支持了腺苷作用阻断对早产儿有益的观点。与对出生后大脑的不利影响相比，腺苷通过A1ARs起作用，在保护胚胎免受缺氧方面发挥重要作用。胚胎保护作用被咖啡因阻断，怀孕早期摄入咖啡因会增加流产和胎儿生长迟缓的风险。腺苷及其拮抗剂在哺乳动物发育过程中起重要的调节作用。腺苷的保护和有害作用取决于暴露的时间和作用的靶位点。
Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methlyxanthines caffeine and theophylline. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). In the postnatal period, A1AR activation may contribute to white matter injury in the preterm infant by altering oligodendrocyte (OL) development. In models of perinatal brain injury, caffeine is neuroprotective against periventricular white matter injury (PWMI) and hypoxic-ischemic encephalopathy (HIE). Supporting the notion that blockade of adenosine action is of benefit in the premature infant, caffeine reduces the incidence of broncho-pulmonary dysplasia and cerebral palsy in clinical studies. In comparison with the adverse effects on the postnatal brain, adenosine acts via A1ARs to play an essential role in protecting the embryo from hypoxia. Embryo protective effects are blocked by caffeine, and caffeine intake during early pregnancy increases the risk of miscarriage and fetal growth retardation. Adenosine and adenosine antagonists play important modulatory roles during mammalian development. The protective and deleterious effects of adenosine depend on the time of exposure and target sites of action.