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）的破坏，这种损伤会破坏发育性髓鞘形成的正常进程。早产儿护理的进步已导致WMI严重程度的持续降低，WMI的严重程度已从较严重的局灶性坏死性病变转变为较轻度的弥漫性WMI。尽管如此，WMI仍然是一个全球性的健康问题，也是由脑瘫和各种神经行为障碍引起的慢性神经系统疾病的最常见原因。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氧化应激和其他侮辱触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性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了OL谱系成熟和髓鞘形成的正常进程。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，尽管存在许多完整的轴突，但新生成的preOLs仍无法沿其正常发育轨迹分化和启动髓鞘形成。破裂的preOL成熟伴随弥漫性神经胶质细胞增生和细胞外基质组成的紊乱，并且部分地由源自反应性星形胶质细胞的抑制因子介导。涉及髓鞘破坏的信号传导途径包括由Notch，WNT-β连环蛋白和透明质酸介导的那些。因此，存在用于干预以促进白质修复和髓鞘形成并可能逆转WMI伴随的脑灰质生长的广泛干扰的潜在广阔但仍定义不清的发展窗口。