Development of microglia in the cerebral white matter of the human fetus and infant
Development of microglia in the cerebral white matter of the human fetus and infant
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DOI：
10.1002/cne.20991
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发表时间：
2006-07-10
影响因子：
2.5
通讯作者：
Kinney, Hannah C.
中科院分区：
文献类型：
--
作者：
Billiards, Saraid S.;Haynes, Robin L.;Kinney, Hannah C.
虽然小胶质细胞激活可能是对多种损伤的一种初始有益反应，但长时间激活会释放有毒物质并导致细胞死亡。在未成熟脑白质中继发于缺氧缺血和/或感染的小胶质细胞激活在脑室周围白质软化症（PVL）的发病机制中很重要，PVL是早产儿脑瘫的主要病理基础。我们假设在PVL易损性高峰窗口期，人胎儿脑白质中激活的小胶质细胞密度会正常出现短暂性过表达。这种增加可能使该区域易受导致小胶质细胞长时间激活的损伤影响，正如PVL中所描述的那样。为了研究人胎儿和婴儿大脑中小胶质细胞的发育情况，我们对23例受孕后20至183周的对照（非PVL）病例使用了小胶质细胞特异性标记物进行免疫细胞化学研究。用于识别小胶质细胞形态的番茄凝集素显示，人胎儿和婴儿的脑白质中密集分布着中间型和阿米巴样小胶质细胞；后者表明处于激活状态。用CD68进行的定量分析显示，相对于新生儿/婴儿（≥37受孕周）以及两个年龄组的上方皮质，胎儿（<37受孕周）脑白质中激活的小胶质细胞密度增加（P = 0.01）。胎儿脑白质中CD68激活的小胶质细胞存在短暂的、依赖发育的过度增多这一主要发现表明，该区域可能因多种以小胶质细胞激活为特征的脑损伤，特别是PVL，而处于一种潜在的“致敏”状态。
Although microglial activation may be an initial beneficial response to a variety of insults, prolonged activation can release toxic substances and lead to cell death. Microglial activation secondary to hypoxia-ischemia and/or infection in immature cerebral white matter is important in the pathogenesis of periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in the premature infant. We hypothesize that a transient overexpression in activated microglial density occurs normally in the cerebral white matter of the human fetus during the peak window of vulnerability for PVL. Such an increase could render this region susceptible to insults that cause prolonged microglial activation, as conceptualized in PVL. To examine the developmental profile of microglia in the human fetus and infant brain, immunocytochemistry with microglial specific markers were used in 23 control (non-PVL) cases ranging from 20 to 183 postconceptional (PC) weeks. Tomato lectin, used to identify microglial morphology, revealed that the cerebral white matter of the human fetus and infant is densely populated with intermediate and amoeboid microglia; the latter is indicative of an activated state. Quantitative analysis with CD68 showed increased density of activated microglia in the cerebral white matter of the fetus (< 37 PC weeks) relative to the neonate/infant (>= 37 PC weeks) and to the overlying cortex of either age group (P = 0.01). The primary finding of a transient, developmental-dependent overabundance of CD68-activated microglia in the cerebral white matter of the fetus suggests a potential "priming" of this area for diverse brain insults characterized by activation of microglia, particularly PVL.