Alart Jon Ander, Álvarez Antonia, Catalan Ana, Herrero de la Parte Borja, Alonso-Alconada Daniel
Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
Psychiatry Department, OSI Bilbao-Basurto, Basurto University Hospital, 48013 Bilbao, Spain.
Antioxidants (Basel). 2024 Sep 16;13(9):1122. doi: 10.3390/antiox13091122.
Neonatal hypoxia-ischemia is a major cause of infant death and disability. The only clinically accepted treatment is therapeutic hypothermia; however, cooling is less effective in the most severely encephalopathic infants. Here, we wanted to test the neuroprotective effect of the antioxidant dimethyl fumarate after severe hypoxia-ischemia in neonatal rats. We used a modified Rice-Vannucci model to generate severe hypoxic-ischemic brain damage in day 7 postnatal rats, which were randomized into four experimental groups: Sham, Sham + DMF, non-treated HI, and HI + DMF. We analyzed brain tissue loss, global and regional (cortex and hippocampus) neuropathological scores, white matter injury, and microglial and astroglial reactivity. Compared to non-treated HI animals, HI + DMF pups showed a reduced brain area loss ( = 0.0031), an improved neuropathological score ( = 0.0016), reduced white matter injuries by preserving myelin tracts ( < 0.001), and diminished astroglial ( < 0.001) and microglial ( < 0.01) activation. After severe hypoxia-ischemia in neonatal rats, DMF induced a strong neuroprotective response, reducing cerebral infarction, gray and white matter damage, and astroglial and microglial activation. Although further molecular studies are needed and its translation to human babies would need to evaluate the molecule in piglets or lambs, DMF may be a potential treatment against neonatal encephalopathy.
新生儿缺氧缺血是婴儿死亡和残疾的主要原因。临床上唯一被认可的治疗方法是治疗性低温；然而，对于脑病最严重的婴儿，降温效果较差。在此，我们想测试抗氧化剂富马酸二甲酯在新生大鼠严重缺氧缺血后对神经的保护作用。我们使用改良的赖斯 - 万努奇模型在出生后第7天的大鼠中造成严重的缺氧缺血性脑损伤，将其随机分为四个实验组：假手术组、假手术 + 富马酸二甲酯组、未治疗的缺氧缺血组和缺氧缺血 + 富马酸二甲酯组。我们分析了脑组织损失、整体和区域（皮质和海马体）神经病理学评分、白质损伤以及小胶质细胞和星形胶质细胞反应性。与未治疗的缺氧缺血动物相比，缺氧缺血 + 富马酸二甲酯组的幼崽脑面积损失减少（ = 0.0031），神经病理学评分改善（ = 0.0016），通过保留髓鞘减少了白质损伤（ < 0.001），星形胶质细胞（ < 0.001）和小胶质细胞（ < 0.01）激活减少。在新生大鼠严重缺氧缺血后，富马酸二甲酯诱导了强烈的神经保护反应，减少了脑梗死、灰质和白质损伤以及星形胶质细胞和小胶质细胞激活。尽管需要进一步的分子研究，并且将其应用于人类婴儿需要在仔猪或羔羊中评估该分子，但富马酸二甲酯可能是治疗新生儿脑病的一种潜在疗法。
