Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Instituto de Investigación Puerta de Hierro Majadahonda, Madrid, Spain.
Pediatr Res. 2019 Mar;85(4):539-545. doi: 10.1038/s41390-019-0282-2. Epub 2019 Jan 16.
Newborn pigs offer theoretical advantages for studying newborn hypoxic-ischemic (HI) brain damage because of a development and structure similar to the human brain. However, the correlation between functional features and actual HI brain damage has not been reported.
Newborn pigs were examined daily for 3 days after a HI insult using amplitude-integrated EEG (aEEG), and a neurobehavioral score enriched with stress and social and object interaction-driven activity evaluation. Brain damage was then assessed using histologic, immunohistochemical, and proton magnetic resonance spectroscopy studies. Brain concentration of several neurotransmitters was determined by HPLC.
HI insult led to aEEG amplitude decrease, muscle tone and activity impairment, eating disorders, poor environmental interaction, and increased motionless periods. Basal aEEG amplitude, muscle tone, and general behavior were the best predictive items for histological and biochemical (lactate/N-acetylaspartate ratio) brain damage. Hyperexcitable response to stress correlated inversely with brain damage. Motionless time, which correlated with brain damage severity, was inversely related to brain concentration of dopamine and norepinephrine.
Standard neurologic examination of brain activity and motor and behavioral performance of newborn pigs is a valuable tool to assess HI brain damage, thus offering a powerful translational model for HI brain damage pathophysiology and management studies.
新生猪由于其大脑发育和结构与人类相似,因此为研究新生儿缺氧缺血性(HI)脑损伤提供了理论优势。然而,功能特征与实际 HI 脑损伤之间的相关性尚未报道。
HI 损伤后,通过振幅整合脑电图(aEEG)对新生猪进行每日检查,共 3 天,并对其应激、社会和物体互动驱动活动评估进行神经行为评分。然后使用组织学、免疫组织化学和质子磁共振波谱研究评估脑损伤。通过 HPLC 测定几种神经递质的脑浓度。
HI 损伤导致 aEEG 幅度降低、肌肉张力和活动障碍、饮食失调、环境互动不良和静止期增加。基础 aEEG 幅度、肌肉张力和一般行为是组织学和生化(乳酸/N-乙酰天冬氨酸比值)脑损伤的最佳预测指标。对压力的过度反应与脑损伤呈负相关。与脑损伤严重程度相关的静止时间与多巴胺和去甲肾上腺素的脑浓度呈负相关。
对新生猪脑活动和运动及行为表现进行标准神经检查是评估 HI 脑损伤的有效工具,为 HI 脑损伤的病理生理学和管理研究提供了有力的转化模型。