Herrera María I, Udovin Lucas D, Toro-Urrego Nicolás, Kusnier Carlos F, Luaces Juan P, Capani Francisco
Centro de Investigaciones en Psicología y Psicopedagogía, Facultad de Psicología, Universidad Católica Argentina, Buenos Aires, Argentina.
Instituto de Investigaciones Cardiológicas, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Front Neurosci. 2018 Mar 28;12:145. doi: 10.3389/fnins.2018.00145. eCollection 2018.
Perinatal asphyxia (PA) is an obstetric complication associated with an impaired gas exchange. This health problem continues to be a determinant of neonatal mortality and neurodevelopmental disorders. Palmitoylethanolamide (PEA) has exerted neuroprotection in several models of brain injury and neurodegeneration. We aimed at evaluating the potential neuroprotective role of PEA in an experimental model, which induces PA in the immature rat brain. PA was induced by placing newborn rats in a water bath at 37°C for 19 min. Once their physiological conditions improved, they were given to surrogate mothers that had delivered normally within the last 24 h. The control group was represented by non-fostered vaginally delivered pups, mimicking the clinical situation. Treatment with PEA (10 mg/kg) was administered within the first hour of life. Modifications in the hippocampus were analyzed with conventional electron microscopy, immunohistochemistry (for NeuN, pNF-H/M, MAP-2, and GFAP) and western blot (for pNF H/M, MAP-2, and GFAP). Behavior was also studied throughout Open Field (OF) Test, Passive Avoidance (PA) Task and Elevated Plus Maze (EPM) Test. After 1 month of the PA insult, we observed neuronal nucleus degeneration in CA1 using electron microscopy. Immunohistochemistry revealed a significant increase in pNF-H/M and decrease in MAP-2 in CA1 reactive area. These changes were also observed when analyzing the level of expression of these markers by western blot. Vertical exploration impairments and anxiety-related behaviors were encountered in the OF and EPM tests. PEA treatment attenuated PA-induced hippocampal damage and its corresponding behavioral alterations. These results contribute to the elucidation of PEA neuroprotective role after PA and the future establishment of therapeutic strategies for the developing brain.
围产期窒息（PA）是一种与气体交换受损相关的产科并发症。这一健康问题仍然是新生儿死亡率和神经发育障碍的一个决定因素。棕榈酰乙醇酰胺（PEA）在几种脑损伤和神经退行性变模型中发挥了神经保护作用。我们旨在评估PEA在诱导未成熟大鼠脑PA的实验模型中的潜在神经保护作用。通过将新生大鼠置于37°C水浴中19分钟来诱导PA。一旦它们的生理状况改善，就将它们交给在过去24小时内正常分娩的代孕母鼠。对照组由未寄养的经阴道分娩的幼崽组成，模拟临床情况。在出生后第一小时内给予PEA（10mg/kg）治疗。用传统电子显微镜、免疫组织化学（针对NeuN、pNF-H/M、MAP-2和GFAP）和蛋白质印迹法（针对pNF H/M、MAP-2和GFAP）分析海马体的变化。还通过旷场（OF）试验、被动回避（PA）任务和高架十字迷宫（EPM）试验对行为进行了研究。在PA损伤1个月后，我们通过电子显微镜观察到CA1区神经元细胞核变性。免疫组织化学显示CA1反应区pNF-H/M显著增加，MAP-2减少。通过蛋白质印迹法分析这些标志物的表达水平时也观察到了这些变化。在OF和EPM试验中出现了垂直探索障碍和焦虑相关行为。PEA治疗减轻了PA诱导的海马损伤及其相应的行为改变。这些结果有助于阐明PA后PEA的神经保护作用以及未来为发育中的大脑建立治疗策略。
