Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland ; Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne, Switzerland.
Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
Ann Clin Transl Neurol. 2014 Dec;1(12):955-67. doi: 10.1002/acn3.138. Epub 2014 Dec 2.
Lactoferrin (Lf) is an iron-binding glycoprotein secreted in maternal milk presenting anti-inflammatory and antioxidant properties. It shows efficient absorption into the brain from nutritional source. Brain injury frequently resulting from cerebral hypoxia-ischemia (HI) has a high incidence in premature infants with ensuing neurodevelopmental disabilities. We investigated the neuroprotective effect of maternal nutritional supplementation with Lf during lactation in a rat model of preterm HI brain injury using magnetic resonance imaging (MRI), brain gene, and protein expression.
Moderate brain HI was induced using unilateral common carotid artery occlusion combined with hypoxia (6%, 30 min) in the postnatal day 3 (P3) rat brain (24-28 weeks human equivalent). High-field multimodal MRI techniques were used to investigate the effect of maternal Lf supplementation through lactation. Expression of cytokine coding genes (TNF-α and IL-6), the prosurvival/antiapoptotic AKT protein and caspase-3 activation were also analyzed in the acute phase after HI.
MRI analysis demonstrated reduced cortical injury in Lf rats few hours post-HI and in long-term outcome (P25). Lf reduced HI-induced modifications of the cortical metabolism and altered white matter microstructure was recovered in Lf-supplemented rats at P25. Lf supplementation significantly decreased brain TNF-α and IL-6 gene transcription, increased phosphorylated AKT levels and reduced activation of caspase-3 at 24 h post-injury.
Lf given through lactation to rat pups with cerebral HI injury shows neuroprotective effects on brain metabolism, and cerebral gray and white matter recovery. This nutritional intervention may be of high interest for the clinical field of preterm brain neuroprotection.
乳铁蛋白（Lf）是一种在母乳中分泌的铁结合糖蛋白，具有抗炎和抗氧化特性。它可以从营养源有效吸收到大脑。早产儿经常因脑缺氧缺血（HI）而导致脑损伤，且伴有较高的神经发育障碍发生率。我们使用磁共振成像（MRI）、脑基因和蛋白质表达来研究哺乳期母亲营养补充 Lf 对早产 HI 脑损伤大鼠模型的神经保护作用。
在新生后第 3 天（P3）大鼠脑（相当于 24-28 周人类）中使用单侧颈总动脉闭塞联合缺氧（6%，30 min）来诱导中度脑 HI。使用高场多模态 MRI 技术来研究哺乳期母亲 Lf 补充的效果。还分析了 HI 后急性期细胞因子编码基因（TNF-α和 IL-6）、存活/抗凋亡 AKT 蛋白和半胱天冬酶-3 的表达。
MRI 分析表明，HI 后数小时和长期结果（P25）中，Lf 组皮质损伤减少。Lf 减少了 HI 诱导的皮质代谢改变，补充 Lf 的大鼠在 P25 时恢复了白质微观结构的改变。Lf 补充显著降低了脑 TNF-α和 IL-6 基因转录，增加了磷酸化 AKT 水平，并减少了损伤后 24 小时 caspase-3 的激活。
给予哺乳期 HI 损伤大鼠的 Lf 显示出对大脑代谢以及大脑灰质和白质恢复的神经保护作用。这种营养干预可能对早产儿脑神经保护的临床领域具有重要意义。
