Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
Ann Neurol. 2012 Mar;71(3):397-406. doi: 10.1002/ana.22612.
The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility is that damage to white matter and subplate neurons that are critical to the formation of the cerebral cortex occurs in conjunction with oligodendrocyte and axonal injury in PVL. We tested the hypothesis that the overall density of neurons in the white matter and subplate region is significantly lower in PVL cases compared to non-PVL controls.
We used a computer-based method for the determination of the density of microtubule-associated protein 2-immunolabeled neurons in the ventricular/subventricular region, periventricular white matter, central white matter, and subplate region in PVL cases and controls.
There were 5 subtypes of subcortical neurons: granular, unipolar, bipolar, inverted pyramidal, and multipolar. The neuronal density of the granular neurons in each of the 4 regions was 54 to 80% lower (p≤0.01) in the PVL cases (n=15) compared to controls adjusted for age and postmortem interval (n=10). The overall densities of unipolar, bipolar, multipolar, and inverted pyramidal neurons did not differ significantly between the PVL cases and controls. No granular neurons expressed markers of neuronal and glial immaturity (Tuj1, doublecortin, or NG2).
These data suggest that quantitative deficits in susceptible granular neurons occur in the white matter distant from periventricular foci, including the subplate region, in PVL, and may contribute to abnormal cortical formation and cognitive dysfunction in preterm survivors.
脑室周围白质软化症（PVL）早产儿认知功能异常的细胞基础尚不清楚。一个重要的可能性是，与 PVL 中的少突胶质细胞和轴突损伤同时发生的是对皮质形成至关重要的白质和基板神经元的损伤。我们检验了这样一个假设，即在 PVL 病例中，与非-PVL 对照相比，白质和基板区域的神经元总体密度明显降低。
我们使用基于计算机的方法来确定脑室/室下区、脑室周围白质、中央白质和基板区中微管相关蛋白 2 免疫标记神经元的密度，在 PVL 病例和对照组中。
有 5 种亚型的皮质下神经元：颗粒状、单极、双极、倒置金字塔形和多极。在 4 个区域中的每个区域中，颗粒状神经元的神经元密度在 PVL 病例（n=15）中比对照（n=10）调整年龄和死后间隔后低 54%至 80%（p≤0.01）。在 PVL 病例和对照组之间，单极、双极、多极和倒置金字塔形神经元的总体密度没有显著差异。没有颗粒状神经元表达神经元和神经胶质未成熟的标志物（Tuj1、双皮质素或 NG2）。
这些数据表明，在 PVL 中，远离脑室周围病灶的白质中，包括基板区域，易感颗粒状神经元的数量存在定量缺陷，这可能导致早产儿幸存者皮质形成异常和认知功能障碍。
