Centre for the Developing Brain, Department of Perinatal Imaging and Health, Division of Imaging & Biomedical Engineering, The Rayne Institute, King's College London, St Thomas' Hospital, London, UK.
Pediatr Res. 2013 Mar;73(3):301-9. doi: 10.1038/pr.2012.186. Epub 2012 Dec 7.
The periventricular white matter (PVWM) of the immature preterm brain is selectively vulnerable to a spectrum of injury. Although essential for normal brain development, the presence of resident microglia may exacerbate PVWM injury.
We used immunohistochemistry to investigate microglia profile in human preterm noninjured control brains and in brains with evidence of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH), with median gestational age (GA) of 24.1 and 25.4 wk, respectively.
The number of microglia in the PVWM was higher than the other brain regions in both the control and GMH/IVH groups. Microglial density increased further in the PVWM of GMH/IVH brains, regardless of hemorrhage severity and despite normal macroscopic and imaging appearances to the PVWM. This was due to an increase in activated Iba1/CD68- and not Iba/CD45-immunopositive microglia. However, there were very few CD68/Ki67 colocalized cells, suggesting that the source of this increase may be due to a quick transformation of CD45-immunopositive hematopoietic microglia into CD68-immunopositive microglia. There was also increased apoptosis in the PVWM of all cases of GMH/IVH, with axonal injury and increased tumor necrosis factor-α (TNF-α) expression evident in the most severe cases.
Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.
未成熟早产儿的脑室周围白质（PVWM）对一系列损伤具有选择性易损性。尽管对正常脑发育至关重要，但驻留的小胶质细胞的存在可能会加重 PVWM 损伤。
我们使用免疫组织化学方法研究了人早产儿非损伤对照脑和伴有生发基质出血/脑室出血（GMH/IVH）证据的脑中小胶质细胞的特征，中位胎龄（GA）分别为 24.1 周和 25.4 周。
在对照和 GMH/IVH 组中，PVWM 中的小胶质细胞数量均高于其他脑区。无论出血严重程度如何，GMH/IVH 脑的 PVWM 中小胶质细胞密度进一步增加，尽管 PVWM 宏观和影像学表现正常。这是由于激活的 Iba1/CD68-而非 Iba/CD45-阳性小胶质细胞增加所致。然而，CD68/Ki67 共定位细胞很少，表明这种增加的来源可能是由于 CD45 阳性造血小胶质细胞迅速转化为 CD68 阳性小胶质细胞。GMH/IVH 的所有病例的 PVWM 中均存在凋亡增加，最严重的病例中可见轴突损伤和肿瘤坏死因子-α（TNF-α）表达增加。
孤立性 GMH/IVH 可能会影响正在进行的脑发育，小胶质细胞的激活起着重要作用。
