Tuzun Funda, Kumral Abdullah, Dilek Mustafa, Ozbal Seda, Ergur Bekir, Yesilirmak Didem Cemile, Duman Nuray, Yilmaz Osman, Ozkan Hasan
Department of Pediatrics, Division of Neonatology, Dokuz Eylul University, Izmir, Turkey.
J Matern Fetal Neonatal Med. 2012 Jun;25(6):849-54. doi: 10.3109/14767058.2011.587917. Epub 2011 Sep 6.
Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants, and no specific treatment currently exists for this condition. We have evaluated whether maternal omega-3 fatty acid (ω3 FA) treatment reduces endotoxin-induced PVL in the developing rat brain.
Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in ω3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered consecutively on the 18th and 19th embryonic days to establish the endotoxin-induced PVL rat model. The animals were divided into four groups: (i) control, (ii) PVL, (iii) PVL+low-dose ω3 FA and (iv) PVL+high-dose ω3 FA. At day P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments.
High-dose maternal ω3 FA treatment reduced brain weight loss. Maternal ω3 FA treatment given either in low or high doses greatly decreased caspase-3 immunoreactivity and increased myelin basic protein immunoreactivity, indicating a decrease in apoptosis and hypomyelination.
Considering that no specific treatment is available for PVL, maternal ω3 FA supplementation may provide a nutritional strategy to limit periventricular white matter damage caused by infections during pregnancy.
脑室周围白质软化（PVL）是早产儿脑损伤的主要形式，目前对此病症尚无特异性治疗方法。我们评估了母体ω-3脂肪酸（ω3 FA）治疗是否能减少发育中大鼠脑内内毒素诱导的PVL。
对孕期确定的Wistar大鼠在妊娠期喂食标准饮食或富含ω3 FA的饮食（70%二十二碳六烯酸+30%二十碳五烯酸混合物）。在胚胎第18天和第19天连续腹腔注射脂多糖（LPS）以建立内毒素诱导的PVL大鼠模型。动物被分为四组：（i）对照组，（ii）PVL组，（iii）PVL+低剂量ω3 FA组和（iv）PVL+高剂量ω3 FA组。在出生后第7天，通过免疫组织化学评估脑室周围白质中的细胞凋亡和髓鞘形成减少情况。
高剂量母体ω3 FA治疗减轻了脑重量损失。低剂量或高剂量的母体ω3 FA治疗均大大降低了半胱天冬酶-3免疫反应性并增加了髓鞘碱性蛋白免疫反应性，表明细胞凋亡和髓鞘形成减少。
鉴于PVL尚无特异性治疗方法，母体补充ω3 FA可能提供一种营养策略，以限制孕期感染引起的脑室周围白质损伤。
