Departments of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Pediatr Res. 2011 Jan;69(1):62-7. doi: 10.1203/PDR.0b013e3181ff3792.
Periventricular leukomalacia (PVL) in the premature infant represents the major substrate underlying cognitive deficits and cerebral palsy and is characterized as focal periventricular necrosis and diffuse gliosis in the immature cerebral white matter. We have recently shown a significant decrease in the density of neurons in PVL relative to controls throughout the white matter, including the subventricular, periventricular, and subcortical regions. These neurons are likely to be remnants of the subplate and/or GABAergic neurons in late migration to the cerebral cortex, both of which are important for proper cortical circuitry in development and throughout adulthood. Here, we tested the hypothesis that intrinsic repair occurs in PVL to attempt to compensate for the deficits in white matter neurons. By using doublecortin (DCX) immunopositivity as a marker of postmitotic migrating neurons, we found significantly increased densities (p < 0.05) of DCX-immunopositive cells in PVL cases (n = 9) compared with controls (n = 7) in the subventricular zone (their presumed site of origin), necrotic foci, and subcortical white matter in the perinatal time-window, i.e. 35-42 postconceptional weeks. These data provide the first evidence suggestive of an attempt at neuronal repair or regeneration in human neonatal white matter injury.
早产儿脑室周围白质软化症 (PVL) 是认知功能障碍和脑瘫的主要基础，其特征为未成熟脑白质中局灶性脑室周围坏死和弥漫性神经胶质增生。我们最近发现，与对照组相比，PVL 患者的白质中神经元密度明显降低，包括室管膜下区、脑室周围区和皮质下区。这些神经元可能是基板残余物和/或晚期迁移到大脑皮层的 GABA 能神经元，两者对于发育过程中和整个成年期皮质电路的正常功能都很重要。在这里，我们检验了这样一个假设，即 PVL 中存在内在修复，以试图弥补白质神经元的缺陷。通过使用双皮质素 (DCX) 免疫阳性作为放射状迁移神经元的标志物，我们发现与对照组 (n = 7) 相比，PVL 病例 (n = 9) 在脑室下区 (其推测的起源部位)、坏死灶和围产期时间窗 (即妊娠后 35-42 周) 的皮质下白质中，DCX 免疫阳性细胞的密度显著增加 (p < 0.05)。这些数据首次提供了人类新生儿脑白质损伤中神经元修复或再生尝试的证据。
