Periventricular leukomalacia: Overview and recent findings
Periventricular leukomalacia: Overview and recent findings
复制标题
DOI：
10.2350/06-01-0024.1
复制
发表时间：
2006-01-01
影响因子：
1.9
通讯作者：
Folkerth, Rebecca D.
中科院分区：
文献类型：
--
作者：
Folkerth, Rebecca D.
脑室周围白质软化症（PVL）是脑瘫的主要底物，其特征是脑深部白质弥漫性损伤，最严重时伴有局灶性坏死。PVL的经典神经病理学引起了关于其发病机制的几种假设，主要与患病早产儿的缺氧缺血再灌注有关。这些包括自由基损伤、细胞因子毒性（特别是考虑到PVL与母胎感染的流行病学关联）和兴奋毒性。最近在人类死后组织中直接发现，PVL中脂质过氧化（羟基壬烯醛和丙二醛）和蛋白质硝化（硝基酪氨酸）的免疫细胞化学标志物显著增加。在PVL易感期（妊娠后24至34周），髓鞘前少突胶质细胞主要存在于心室周围区域，是自由基损伤的目标，并遭受细胞死亡。易感性可归因于，至少部分，相对缺乏超氧化物歧化酶在早产儿白质，包括髓鞘前少突胶质细胞。一些细胞因子，包括干扰素- γ（已知在体外对未成熟的少突胶质细胞有直接毒性），以及肿瘤坏死因子-oc和白细胞介素2和6，已经在PVL中被证实。小胶质细胞表达对细菌产物如脂多糖的toll样受体，在PVL白质中增加，可能导致损伤。初步的研究表明谷氨酸受体和谷氨酸转运体在PVL中的作用，正如在实验动物中所看到的那样。这些发现为PVL的最终治疗或预防策略铺平了道路。
Periventricular leukomalacia (PVL), the main substrate for cerebral palsy, is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The classic neuropathology of PVL has given rise to several hypotheses about the pathogenesis, largely relating to hypoxia-ischemia and reperfusion in the sick premature infant. These include free radical injury, cytokine toxicity (especially given the epidemiologic association of PVL with maternofetal infection), and excitotoxicity. Among the recent findings directly in human postmortem tissue is that immunocytochemical markers of lipid peroxidation (hydroxy-nonenal and malondialdehyde) and protein nitration (nitrotyrosine) are significantly increased in PVL. Premyelinating oligodendrocytes, which predominate in periventricular regions during the window of vulnerability to PVL (24 to 34 postconceptional weeks), are the targets of this free radical injury, and suffer cell death. Susceptibility can be attributed, at least in part, to a relative deficiency of superoxide dismutases in the preterm white matter, including premyelinating oligodendrocytes. Several cytokines, including interferon-gamma (known to be directly toxic to immature oligodendroglia in vitro), as well as tumor necrosis factor-oc and interleukins 2 and 6, have been demonstrated in PVL. Microglia, which express toll-like receptors to bacterial products such as lipopolysaccharide, are increased in PVL white matter and may contribute to the injury. Preliminary work suggests a role for glutamate receptors and glutamate transporters in PVL, as has been seen in experimental animals. These findings pave the way for eventual therapeutic or preventive strategies for PVL.