New horizons for newborn brain protection: enhancing endogenous neuroprotection.
New horizons for newborn brain protection: enhancing endogenous neuroprotection.
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DOI：
10.1136/archdischild-2014-306284
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Robertson NJ
中科院分区：
文献类型：
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作者：
Hassell KJ;Ezzati M;Alonso-Alconada D;Hausenloy DJ;Robertson NJ
产时相关事件是全球儿童死亡的第三大原因，每年导致 100 万神经残疾幸存者。遭受围产期损伤的婴儿通常会出现新生儿脑病 (NE)。单纯缺氧缺血 (HI) 对 NE 的影响一直存在争议。在过去的十年中，人们认识到炎症在 NE 和神经功能障碍病因学中的致敏作用。在高收入国家，低温治疗是 NE 的标准护理；然而，它对患有败血症的脑病婴儿或绒毛膜羊膜炎后出生的婴儿的益处尚不清楚。现在人们认识到，脑损伤的阶段延伸到第三阶段，该阶段在最初的损伤后持续数周至数年，并为治疗开辟了新的可能性。最近的重点是了解内源性神经保护，以及一旦发生像 NE 那样的大脑损伤，如何在治疗上增强它或补充其效应器。在这篇综述中，我们重点关注可以增强人体自身内源性神经保护的策略。我们特别讨论远程缺血后处理，通过在缺氧缺血损伤后立即开始缺氧/再灌注刺激，可以激活内源性脑耐受性。治疗性低温、褪黑激素、促红细胞生成素和大麻素是我们补充HI内源性反应以获得其全部神经保护潜力的方法的例子。根据损伤的性质和阶段在正确的时间实现干预措施的正确平衡将是未来十年的重大挑战。
Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy. There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade.