Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS One. 2013 Dec 11;8(12):e82940. doi: 10.1371/journal.pone.0082940. eCollection 2013.
Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate.
We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter.
A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI.
Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI.
尽管早产儿围产期脑白质损伤（WMI）的范围已从囊状脑软化转变为更轻微的 WMI 形式，但导致这种变化的原因尚不清楚。我们假设，通过炎症的免疫组织化学标志物量化的 WMI 变异性可以与血氧、葡萄糖和乳酸水平受损的严重程度相关。
我们使用了一种在子宫内中等程度缺氧和全球严重但不完全性脑缺血的早产胎儿羊模型，该模型再现了人类 WMI 的范围。由于在闭塞期间仍有少量但可测量的脑血流，我们试图确定残留动脉血流的代谢状态是否与 WMI 的严重程度相关。在缺氧-缺血接近尾声时，我们记录了头部动脉血压、血氧、葡萄糖和乳酸水平。为了定义 WMI 的范围，我们将有序的 WMI 评分量表与无偏的定量图像分析方案进行了比较，该方案为整个白质的星形胶质细胞增生和小胶质细胞增生提供了连续的组织病理学结果测量。
观察到 WMI 范围从弥漫性非坏死性病变到更严重的损伤，包括微观或宏观坏死的离散焦点。残留动脉压、氧含量和血糖与 WMI 呈显著负相关，而乳酸浓度则呈正相关。葡萄糖水平升高与 WMI 程度较轻最显著相关。
我们的结果表明，在缺氧和严重头部低血压的情况下，使用无偏免疫组织化学测量测量的 WMI 严重程度与包括葡萄糖在内的几种生理参数相关，葡萄糖可能是胎儿对缺氧反应的有用标志物，或提供对能量衰竭和更严重 WMI 的保护。
