The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Diffuse WMI involves maturation-dependent vulnerability of the oligodendrocyte (OL) lineage with selective degeneration of late oligodendrocyte progenitors (preOLs) triggered by oxidative stress and other insults. The magnitude and distribution of diffuse WMI are related to both the timing of appearance and regional distribution of susceptible preOLs. Diffuse WMI disrupts the normal progression of OL lineage maturation and myelination through aberrant mechanisms of regeneration and repair. PreOL degeneration is accompanied by early robust proliferation of OL progenitors that regenerate and augment the preOL pool available to generate myelinating OLs. However, newly generated preOLs fail to differentiate and initiate myelination along their normal developmental trajectory despite the presence of numerous intact-appearing axons. Disrupted preOL maturation is accompanied by diffuse gliosis and disturbances in the composition of the extracellular matrix and is mediated in part by inhibitory factors derived from reactive astrocytes. Signaling pathways implicated in disrupted myelination include those mediated by Notch, WNT-beta catenin, and hyaluronan. Hence, there exists a potentially broad but still poorly defined developmental window for interventions to promote white matter repair and myelination and potentially reverses the widespread disturbances in cerebral gray matter growth that accompanies WMI.

人类早产儿大脑特别容易受到脑白质损伤（WMI）的影响，从而扰乱发育性髓鞘形成的正常进展。早产儿护理的进步导致 WMI 严重程度持续降低，从更严重的局灶性坏死病变转变为更轻微的弥漫性 WMI。尽管如此，WMI 仍然是一个全球性健康问题，也是脑瘫和各种神经行为障碍导致慢性神经系统发病的最常见原因。弥漫性 WMI 涉及少突胶质细胞 (OL) 谱系的成熟依赖性脆弱性，以及由氧化应激和其他损伤引发的晚期少突胶质细胞祖细胞 (preOL) 的选择性变性。弥漫性 WMI 的大小和分布与易感 preOL 的出现时间和区域分布有关。弥漫性 WMI 通过异常的再生和修复机制破坏 OL 谱系成熟和髓鞘形成的正常进展。 PreOL 变性伴随着 OL 祖细胞的早期强劲增殖，这些祖细胞再生并增强了可用于产生髓鞘 OL 的 preOL 库。然而，尽管存在许多外观完整的轴突，但新生成的 preOL 无法沿着其正常发育轨迹分化和启动髓鞘形成。 preOL 成熟的破坏伴随着弥漫性神经胶质增生和细胞外基质组成的紊乱，并且部分是由反应性星形胶质细胞衍生的抑制因子介导的。与髓鞘形成破坏相关的信号通路包括由 Notch、WNT-β 连环蛋白和透明质酸介导的信号通路。 因此，促进白质修复和髓鞘形成的干预措施存在一个潜在广泛但仍不明确的发育窗口，并有可能逆转伴随 WMI 的大脑灰质生长的广泛紊乱。