Dilek Mustafa, Kumral Abdullah, Okyay Emre, Ozbal Seda, Tugyan Kazim, Tuzun Funda, Sever Ali Haydar, Yilmaz Osman, Duman Nuray, Ozkan Hasan
Department of Pediatrics, Division of Neonatology .
J Matern Fetal Neonatal Med. 2013 Dec;26(18):1865-71. doi: 10.3109/14767058.2013.798290. Epub 2013 Jul 23.
To investigate the potential neuroprotective effect of maternal pentoxifylline (PNTX) treatment in endotoxin-induced periventricular leukomalasia (PVL) in the developing rat brain.
Intraperitoneal injection of lipopolysaccharide was administered on two of three Wistar pregnant rats to establish PVL. To obtain PNTX-treated group, one of the two dams were injected with PNTX. The control group was treated with saline. Rat pups were grouped as control, maternal LPS-treated group and PNTX + LPS-treated group. At 7th postnatal days, apoptosis and hypomyelination were evaluated. Apoptosis was evaluated by caspase-3 and terminal deoxynucleotidyl transferase [TdT] dUTP nick endlabelling reaction (TUNEL) immunostaining. To assess hypomyelination, myelin basic protein (MBP) staining, as a marker of myelination, was evaluated.
MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the PNTX-treated group. PNTX treatment significantly reduced the number of apoptotic cells in the periventricular WM shown on Tunel and caspase-3.
Presented study is first indicated that PNTX may provide protection against an LPS-induced inflammatory response and WMI in the developing rat brain. Our results also suggest that PNTX treatment in pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.
研究孕鼠使用己酮可可碱（PNTX）治疗对内毒素诱导的发育中大鼠脑室内白质软化症（PVL）的潜在神经保护作用。
对三只Wistar孕鼠中的两只腹腔注射脂多糖以建立PVL模型。为获得PNTX治疗组，对两只母鼠中的一只注射PNTX。对照组用生理盐水处理。将新生大鼠分为对照组、母鼠LPS处理组和PNTX + LPS处理组。在出生后第7天，评估细胞凋亡和髓鞘形成减少情况。通过半胱天冬酶-3和末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记反应（TUNEL）免疫染色评估细胞凋亡。为评估髓鞘形成减少情况，评估髓鞘碱性蛋白（MBP）染色，其作为髓鞘形成的标志物。
与PNTX治疗组相比，LPS治疗组大鼠脑内MBP染色明显减少且较弱。PNTX治疗显著减少了Tunel和半胱天冬酶-3显示的脑室周围白质中凋亡细胞的数量。
本研究首次表明，PNTX可能对发育中大鼠脑内LPS诱导的炎症反应和白质损伤提供保护。我们的结果还表明，对患有母体或胎盘感染的孕妇进行PNTX治疗可能会将PVL和脑瘫的风险降至最低。
