Diffuse axonal injury in Periventricular Leukomalacia as determined by apoptotic marker fractin
Diffuse axonal injury in Periventricular Leukomalacia as determined by apoptotic marker fractin
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DOI：
10.1203/pdr.0b013e31816c825c
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Kinney, Hannah C.
中科院分区：
文献类型：
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作者：
Haynes, Robin L.;Billiards, Saraid S.;Kinney, Hannah C.
脑室周围白质软化症(PVL)是早产儿神经功能缺陷的主要底物，与脑白质体积减少有关。利用轴突病理的免疫标记物[P-淀粉样前体蛋白(β-APP)和凋亡标记物Fractin]，我们验证了PVL中广泛(弥漫性)轴突损伤发生在坏死灶以外的胶质白质中的假说，从而导致白质体积减少。在17例对照组和13例不同年龄段的PVL患者的队列中，用Fractin检测到PVL周围和远离急性和机化坏死灶的白质部位有弥漫性轴索损害。使用β-APP，在急性期和组织化(亚急性)阶段的坏死灶中检测到轴突球形，这一发现与其他发现一致。有趣的是，在坏死灶的球体中也检测到了GAP-43的表达，这表明试图进行轴突再生。31%的PVL患者有丘脑损害，15%的PVL患者大脑皮质有神经元损害。我们的结论是，由凋亡标记物Fractin确定的弥漫性轴索损伤发生在PVL中，其原因可能包括原发缺血和继发于皮质丘脑神经元损伤的营养性变性。
Periventricular leukomalacia (PVL), the major substrate of neurologic deficits in premature infants, is associated with reduced white matter volume. Using immunomarkers of axonal pathology [P-amyloid precursor protein (beta-APP) and apoptotic marker fractin], we tested the hypothesis that widespread (diffuse) axonal injury occurs in the gliotic white matter beyond the foci of necrosis in PVL, thus contributing to the white matter volume reduction. In a cohort of 17 control cases and 13 PVL cases with lesions of different chronological ages, diffuse axonal damage in PVL was detected by fractin in white matter sites surrounding and distant from acute and organizing foci of necrosis. Using beta-APP, axonal spheroids were detected within necrotic foci in the acute and organizing (subacute) stages, a finding consistent with others. Interestingly, GAP-43 expression was also detected in spheroids in the necrotic foci, suggesting attempts at axonal regeneration. Thirty-one percent of the PVL cases had thalamic damage and 15% neuronal injury in the cerebral cortex overlying PVL. We conclude that diffuse axonal injury, as determined by apoptotic marker fractin, occurs in PVL and that its cause likely includes primary ischemia and trophic degeneration secondary to corticothalamic neuronal damage.