MAGNESIUM SULFATE (MG) PREVENTS MATERNAL INFLAMMATION INDUCED OFFSPRING CEREBRAL INJURY EVIDENT ON MRI BUT NOT VIA IL-1β
MAGNESIUM SULFATE (MG) PREVENTS MATERNAL INFLAMMATION INDUCED OFFSPRING CEREBRAL INJURY EVIDENT ON MRI BUT NOT VIA IL-1β
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DOI：
10.1016/j.neuroscience.2017.03.046
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发表时间：
2017-06-14
期刊：
影响因子：
3.3
通讯作者：
Beloosesky, Ron
中科院分区：
文献类型：
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作者：
Ginsberg, Yuval;Khatib, Nizar;Beloosesky, Ron
目的：由于母亲应用硫酸镁(MG)治疗可能对胎儿大脑有保护作用，我们试图评估MG的炎症相关神经保护作用及其与白细胞介素1β(IL-1β)的关系。方法：妊娠18天的SD大鼠接受腹腔注射。脂多糖(LPS)或生理盐水。大坝被随机分配到S.C.治疗。生理盐水(对照组)，或注射前或注射后的MG。注射，共分三组。治疗结束时，对18只孕鼠(每组6只)的胎脑IL-1β进行定量。另有18只自然分娩的孕鼠和幼鼠被允许成熟。出生后第25天，对雌性后代进行磁共振成像(MRI)检查，并采用基于体素的分析方法进行分析。采用表观扩散系数(ADC)和T2松弛方案评估脑白质和灰质损伤。结果：脂多糖处理组仔鼠表现为(1)脑白质和灰质T2水平显著升高，(2)脑白质和灰质ADC水平升高，与弥漫性脑损伤一致。经MG处理的脂多糖母鼠的后代表现出与对照母鼠相似的T2和ADC水平。胎脑IL-114水平显著高于对照组(0.125±-0.01vs0.100+/-0.01u，p<；0.05)。母体MG患者的IL-1β水平未见明显下降。结论：母体MG可预防母体内毒素所致的新生儿脑损伤。母体MG治疗可能对与母体/胎儿炎症相关的人类分娩有效。MG治疗后胎儿大脑IL-1β水平没有下降，提示MG的机制不是通过抑制IL-1β的产生。意义陈述：胎儿宫内暴露于母体炎症和促炎细胞因子与子代不良神经结局相关。尽管其确切的机制尚不清楚，但硫酸镁(MG)通常用于早产儿脑白质损伤的神经保护。一种拟议的机制涉及MG降低促炎细胞因子水平的能力。在本研究中，我们利用脂多糖诱导的母体炎症大鼠模型，利用磁共振成像技术研究了MG对胎脑IL-1β水平的短期影响及其对子代脑的长期神经保护作用。意义陈述：我们证明了母体给予MG可以预防长期的新生儿脑损伤，但由于胎脑IL-1β水平没有下降，MG的神经保护机制并不是通过抑制IL-1β的产生来实现的。(C)2017年IBRO。爱思唯尔有限公司出版。保留所有权利。
Objective: As maternal treatment with magnesium sulfate (MG) may protect the fetal brain, we sought to assess the inflammation associated neuroprotective potential of MG and its association to interleukin 1 beta (IL-1 beta. Methods: Pregnant Sprague-Dawley rats at 18-day gestation received i.p. lipopolysaccharide (LPS) or saline. Dams were randomized to treatment with s.c. saline (control), or MG prior to or following the i.p. injection, resulting in three groups. At the end of the treatment, fetal brain IL-1 beta was quantified for 18 pregnant rats (six of each group). Another 18 pregnant rats delivered spontaneously and pups were allowed to mature. At postnatal day 25, female offspring were examined by magnetic resonance imaging (MRI) and analyzed using voxel based analysis. Apparent diffusion coefficient (ADC) and T2 relaxation protocols were performed to assess white and gray matter injury. Results: Offspring of LPS-treated dams exhibited (1) significantly increased T2 levels, and (2) increased ADC levels in white and gray matter, consistent with diffuse cerebral injury. Offspring of MG-treated LPS dams demonstrated similar T2 and ADC levels as control dams. Fetal brain IL-114 was significantly increased following maternal LPS compared to control (0.125 +/- 0.01 vs 0.100 +/- 0.01u, p < 0.05). No significant decrease in IL-1 beta level was observed in response to maternal MG. Conclusions: Maternal LPS-induced neonatal brain injury can be prevented by maternal MG. Maternal MG therapy may be effective in human deliveries associated with maternal/fetal inflammation. The absence of a decrease in fetus brain levels of IL-1 beta following MG treatment implies that the mechanism of MG is not through inhibition of IL-1 beta production. Significance statement: Intrauterine fetal exposure to maternal inflammation and pro-inflammatory cytokines is associated with adverse offspring neurological outcomes. Although its precise mechanism is not elucidated, magnesium sulfate (MG) is commonly used as neuroprotection for white matter brain injuries in preterm fetuses. A proposed mechanism involves the ability of MG to reduce pro-inflammatory cytokine levels. In the current study, we used a rat model of LPS-induced maternal inflammation to investigate the short-term effect of MG on fetal brain IL-1 beta levels, and its long-term neuroprotective effect on the offspring brain by using MRI.Significance statement: We demonstrated that maternal administration of MG can prevent long-term neonatal brain injury but, since no decrease was observed in fetal brain IL-1 beta levels, the neuro-protective mechanism of MG is not mediated by inhibition of IL-1 beta production. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.