Back Stephen A
Department of Pediatrics, Oregon Health & Science University, Portland, Oregon; Department of Neurology, Oregon Health & Science University, Portland, Oregon.
Pediatr Neurol. 2015 Sep;53(3):185-92. doi: 10.1016/j.pediatrneurol.2015.04.006. Epub 2015 Apr 18.
Preterm neonates are surviving with a milder spectrum of motor and cognitive disabilities that appear to be related to widespread disturbances in cell maturation that target cerebral gray and white matter. Whereas the preterm brain was previously at high risk for destructive lesions, preterm survivors now commonly display less severe injury that is associated with aberrant regeneration and repair responses that result in reduced cerebral growth. Impaired cerebral white matter growth is related to myelination disturbances that are initiated by acute death of premyelinating oligodendrocytes, but are followed by rapid regeneration of premyelinating oligodendrocytes that fail to normally mature to myelinating cells. Although immature neurons are more resistant to cell death than mature neurons, they display widespread disturbances in maturation of their dendritic arbors and synapses, which further contributes to impaired cerebral growth. Thus, even more mild cerebral injury involves disrupted repair mechanisms in which neurons and premyelinating oligodendrocytes fail to fully mature during a critical window in development of neural circuitry. These recently recognized distinct forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic strategies to promote brain growth and repair.
早产新生儿正带着较轻程度的运动和认知障碍存活下来,这些障碍似乎与针对脑灰质和白质的细胞成熟广泛紊乱有关。虽然早产脑以前极易发生破坏性病变,但早产幸存者现在通常表现出不太严重的损伤,这种损伤与异常的再生和修复反应有关,导致脑生长减缓。脑白质生长受损与少突胶质前体细胞急性死亡引发的髓鞘形成紊乱有关,但随后少突胶质前体细胞迅速再生,却未能正常成熟为髓鞘形成细胞。虽然未成熟神经元比成熟神经元对细胞死亡更具抵抗力,但它们在树突分支和突触成熟方面表现出广泛紊乱,这进一步导致脑生长受损。因此,即使是更轻微的脑损伤也涉及修复机制紊乱,其中神经元和少突胶质前体细胞在神经回路发育的关键窗口期未能完全成熟。这些最近才被认识到的脑灰质和白质发育异常的不同形式带来了新的诊断挑战,并提示了促进脑生长和修复的新治疗策略。