Oxidative injury in the cerebral cortex and subplate neurons in periventricular leukomalacia.
Oxidative injury in the cerebral cortex and subplate neurons in periventricular leukomalacia.
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DOI：
10.1097/nen.0b013e31817e5c5e
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发表时间：
2008-07
影响因子：
3.2
通讯作者：
Haynes RL
中科院分区：
文献类型：
--
作者：
Folkerth RD;Trachtenberg FL;Haynes RL
我们以前确定的免疫细胞化学证据的硝化和氧化损伤的前髓鞘少突胶质细胞在脑室周围白质软化症（PVL）。在这里，我们测试的假设，自由基损伤发生在上覆的大脑皮层和基板神经元PVL。我们对PVL（n = 11）和非PVL（n = 15）病例（孕后34 - 109周）的硝基酪氨酸（NT）、丙二醛（MDA）和羟基壬烯醛（HNE）加合物进行免疫染色，并对神经元染色密度进行评分。控制年龄的协方差分析。PVL病例的平均MDA评分高于对照组（p = 0.005）。HNE评分仅在PVL病例中随年龄增加（诊断与年龄相互作用，p = 0.024）。NT评分没有显著增加。在11个PVL和23个对照病例中，在20和183周之间的受孕后，细胞形态与subplate和Cajal-Retzius神经元一致，显示出定性增加的自由基修饰PVL超过对照病例，在subplate神经元和Cajal-Retzius细胞中HNE和NT的比值比具有统计学意义。反应性星形胶质细胞和小胶质细胞的GFAP和CD 68评分分别没有显著增加，表明炎症反应最小。因此，皮质和“先锋”神经元的氧化/硝化损伤，虽然总体上是轻度的，但可能导致早产儿幸存者的皮质体积损失和认知/行为障碍。
We previously identified immunocytochemical evidence of nitrative and oxidative injury in premyelinating oligodendrocytes in periventricular leukomalacia (PVL). Here, we tested the hypothesis that free radical injury occurs in the overlying cerebral cortex and subplate neurons in PVL. We immunostained for nitrotyrosine (NT), malondialdehyde (MDA), and hydroxynonenal (HNE) adducts and scored neuron staining density in PVL (n = 11) and non-PVL (n = 15) cases (postconceptional ages from 34 to 109 weeks). Analysis of covariance controlled for age. Mean MDA scores in PVL cases were increased over controls (p = 0.005). HNE scores increased with age only in PVL cases (diagnosis versus age interaction, p = 0.024). NT scores were not significantly increased. In 11 PVL and 23 control cases between 20 and 183 postconceptional weeks, cells morphologically consistent with subplate and Cajal-Retzius neurons showed qualitatively increased free radical modification in PVL over control cases with statistically significant odds ratios for HNE and NT in both subplate neurons and Cajal-Retzius cells. GFAP and CD68 scores for reactive astrocytes and microglia, respectively, were not significantly increased, suggesting a minimal inflammatory response. Thus, oxidative/nitrative damage to cortical and “pioneer” neurons, although mild overall, may contribute to cortical volume loss and cognitive/behavioral impairment in survivors of prematurity.