The biological basis of injury and neuroprotection in the fetal and neonatal brain.
The biological basis of injury and neuroprotection in the fetal and neonatal brain.
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DOI：
10.1016/j.ijdevneu.2011.04.004
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发表时间：
2011-10
影响因子：
1.8
通讯作者：
Walker, David
中科院分区：
文献类型：
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作者：
Rees, Sandra;Harding, Richard;Walker, David
关键词：
提供低水平氧气和/或营养物的受损的子宫内环境，或感染或炎症，可导致胎儿脑损伤，脑发育异常，以及在慢性妥协的情况下，子宫内生长受限。早产也可能与发育中的大脑损伤有关，并影响大脑生长的正常轨迹。本次审查将集中在围产期缺氧事件（急性，慢性，与炎症相关或作为早产的前因）可能对发育中的大脑的影响。在这些病症的动物模型中，我们已经发现相对短暂的（急性）胎儿低氧血症期可对胎儿脑具有显著影响，例如易感神经元群体（小脑、海马、皮质）的死亡和脑白色物质损伤。慢性胎盘功能不全，包括胎儿低氧血症、营养限制和内分泌状态改变，可导致胎儿生长受限和神经连接的长期缺陷，以及出生后功能的改变，例如听觉和视觉系统。母体/胎儿炎症可导致胎儿脑损伤，特别是但不限于白色物质;当与胎儿低氧血症相关时，损伤更明显。在狒狒中，正常的生长轨迹受到早产的影响，在氧饱和度的较高通量和更大程度的神经病理损伤之间存在直接相关性。目前，对足月新生儿的新生儿脑病的唯一既定疗法是中度低温，尽管这仅对中度而非严重受影响的大脑提供一定的保护。对于早产儿脑损伤没有公认的治疗方法。因此，寻找更有效的治疗方法仍在继续;我们讨论了神经保护剂（促红细胞生成素，N-乙酰半胱氨酸，褪黑激素，肌酸，神经类固醇），我们已经在适当的动物模型中进行了试验。现在正在考虑将低温与这些药剂或生长因子结合的可能性。更深入地了解脑损伤的因果通路对于开发有效的神经保护策略至关重要。
A compromised intrauterine environment that delivers low levels of oxygen and/or nutrients, or is infected or inflammatory, can result in fetal brain injury, abnormal brain development and in cases of chronic compromise, intrauterine growth restriction. Preterm birth can also be associated with injury to the developing brain and affect the normal trajectory of brain growth. This review will focus on the effects that episodes of perinatal hypoxia (acute, chronic, associated with inflammation or as an antecedent of preterm birth) can have on the developing brain. In animal models of these conditions we have found that relatively brief (acute) periods of fetal hypoxemia can have significant effects on the fetal brain, for example death of susceptible neuronal populations (cerebellum, hippocampus, cortex) and cerebral white matter damage. Chronic placental insufficiency which includes fetal hypoxemia, nutrient restriction and altered endocrine status can result in fetal growth restriction and long-term deficits in neural connectivity in addition to altered postnatal function, for example in the auditory and visual systems. Maternal/fetal inflammation can result in fetal brain damage, particularly but not exclusively in the white matter; injury is more pronounced when associated with fetal hypoxemia. In the baboon, in which the normal trajectory of growth is affected by preterm birth, there is a direct correlation between a higher flux in oxygen saturation and a greater extent of neuropathological damage. Currently, the only established therapy for neonatal encephalopathy in full term neonates is moderate hypothermia although this only offers some protection to moderately but not severely affected brains. There is no accepted therapy for injured preterm brains. Consequently the search for more efficacious treatments continues; we discuss neuroprotective agents (erythropoietin, N-acetyl cysteine, melatonin, creatine, neurosteroids) which we have trialed in appropriate animal models. The possibility of combining hypothermia with such agents or growth factors is now being considered. A deeper understanding of causal pathways in brain injury is essential for the development of efficacious strategies for neuroprotection.
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影响因子：
3
作者：
Cilio, Maria Roberta;Ferriero, Donna M.
通讯作者：
Ferriero, Donna M.
影响因子：
6.4
作者：
Billiards, Saraid S.;Haynes, Robin L.;Kinney, Hannah C.
通讯作者：
Kinney, Hannah C.
影响因子：
1.9
作者：
Back, Stephen A.;Riddle, Art;Hohimer, A. Roger
通讯作者：
Hohimer, A. Roger
影响因子：
105.7
作者：
Badawi, N;Kurinczuk, JJ;Stanley, FJ
通讯作者：
Stanley, FJ
DOI：
10.1038/nri2873
发表时间：
2010-12
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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