Hypoxic and ischemic disorders of infants and children. Lecture for 38th Meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996
Hypoxic and ischemic disorders of infants and children. Lecture for 38th Meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996
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DOI：
10.1016/s0387-7604(96)00561-x
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发表时间：
1997-06-01
影响因子：
1.7
通讯作者：
Johnston, MV
中科院分区：
文献类型：
--
作者：
Johnston, MV
缺氧-缺血损伤了不同年龄段未成熟大脑的特定区域。在妊娠32周之前，脑室周围白质是选择性脆弱的，但在妊娠的最后三个月，基底节变得特别容易受到损伤。缺氧-缺血通过激活一系列生化事件而导致损伤，这些事件在最初的侮辱后几个小时到几天内展开，我们正在研究年龄改变这些事件的方式。这一级联反应包括谷氨酸的释放、兴奋性氨基酸受体的过度刺激和细胞内钙水平的升高。在临床上，这一系列事件表现为缺氧缺血性脑病(HIE)，这是一种包括昏迷、癫痫发作、爆发抑制EEG、呼吸抑制和严重低眼压的综合征。临床研究已经确定了新生儿脑病的严重程度与后来的脑损伤或脑性瘫痪的表现之间的关系。潜在的神经保护疗法需要在受到伤害后给予有效，但大多数N-甲基-D-天冬氨酸(NMDA)谷氨酸拮抗剂在受伤后的“治疗时间窗口”是有限的。采用犬缺氧缺血模型和新生大鼠低温停循环模型，发现伤后6~24小时，基底节区和皮质神经元型一氧化氮合酶(NNOS)免疫组织化学染色明显增强。NNOS的诱导早于神经元最大坏死期和出现大量凋亡核的时间。我们还发现，新生大鼠缺氧缺血后短暂的亚低温(32摄氏度)2小时可使神经元坏死延迟一周以上。我们正在确定这种延迟是否与nNOS激活的变化有关。在损伤后阶段nNOS的诱导可能有助于缺氧缺血性损伤后损伤的表达和脑病的迹象。(C)1997年爱思唯尔科学公司。
Hypoxia-ischemia damages selected regions of the immature brain at different ages. Prior to 32 weeks gestation the periventricular white matter is selectively vulnerable but in the last trimester the basal ganglia become especially vulnerable to injury. Hypoxia-ischemia causes injury by activating a series of biochemical events that unfolds over a period of hours to days following the initial insult and we are investigating the ways in which age modifies these events. The cascade includes release of glutamate, overstimulation of excitatory amino acid receptors and raised intracellular levels of calcium. Clinically this series of events is manifested by hypoxic-ischemic encephalopathy (HIE), a syndrome that includes coma, seizures, a burst suppression EEG, respiratory depression and severe hypotonia. Clinical studies have established a relationship between the severity of neonatal encephalopathy and later manifestations of brain damage or cerebral palsy. Potential neuroprotective therapies need to be effective when given after the insult but the 'therapeutic time window' for most N-methyl-D-asparate (NMDA) glutamate antagonists is limited after injury. Using a model of hypoxic-ischemic injury and neonatal rats and hypothermic-circulatory arrest in dogs, we found that immunohistochemical staining for neuronal nitric oxide synthase (nNOS) is markedly increased from 6 to 24 h after the insult in the basal ganglia and cortex. The induction of nNOS preceded the time of maximal neuronal necrosis and during the time when many apoptotic nuclei were appearing. We have also found that a brief period of 2 h of mild hypothermia (32 degrees C) following hypoxia-ischemia in neonatal rats delayed neuronal necrosis by more than a week. We are determining whether this delay is related to a change in nNOS activation. Induction of nNOS in the post-insult period may contribute to expression of injury and signs of encephalopathy following a hypoxic-ischemic insult. (C) 1997 Elsevier Science B.V.