早产胎羊缺氧缺血后胰岛素样生长因子-1对白质的保护作用

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae373
Guido Wassink, Kenta H T Cho, Sam Mathai, Christopher A Lear, Justin M Dean, Alistair J Gunn, Laura Bennet
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引用次数: 0

摘要

极早产儿围产期缺氧缺血与长期神经发育障碍有关,目前尚无特效疗法。胰岛素样生长因子-1可减轻急性脑损伤,但其对缺氧缺血后慢性脑白质损伤的影响尚不明确。早产胎羊(0.6 胎龄)接受假窒息或脐带闭塞诱导的窒息 30 分钟,窒息后恢复 3 天或 35 天。35天恢复组在窒息后3至14天接受胰岛素样生长因子-1(1微克/24小时)或载体的脑室内输注。窒息与脑室扩大、额叶和顶叶白质面积损失有关(与假窒息相比,P < 0.05)。这与髓鞘碱性蛋白面积减少、少突胶质细胞转录因子2数量减少、脑室周围白质中成熟的抗腺瘤性息肉病大肠杆菌阳性少突胶质细胞数量减少(P < 0.05)、持续炎症和caspase-3活化(P < 0.05)有关。八个胎儿中有四个在颞白质中出现囊性病变。长期输注胰岛素样生长因子-1可恢复额叶白质面积,改善少突胶质细胞转录因子2阳性和成熟的抗腺瘤性息肉病大肠杆菌阳性少突胶质细胞的数量,35天恢复后星形胶质细胞和小胶质细胞减少(与窒息相比,P < 0.05)。四个胎儿中有一个出现颞叶囊性病变。从功能上看,经胰岛素样生长因子-1处理的胎儿脑电图功率恢复较快,但频谱边缘恢复较慢。令人鼓舞的是,这些研究结果表明,延迟、延长胰岛素样生长因子-1治疗可改善极未成熟大脑严重窒息后脑室周围白质的功能成熟,至少部分是通过抑制慢性神经炎症实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
White matter protection with insulin-like growth factor-1 after hypoxia-ischaemia in preterm foetal sheep.

Perinatal hypoxia-ischaemia in extremely preterm infants is associated with long-term neurodevelopmental impairment, for which there is no specific treatment. Insulin-like growth factor-1 can reduce acute brain injury, but its effects on chronic white matter injury after hypoxia-ischaemia are unclear. Preterm-equivalent foetal sheep (0.6 gestation) received either sham-asphyxia or asphyxia induced by umbilical cord occlusion for 30 min, and recovered for either 3 or 35 days after asphyxia. The 35 day recovery groups received either an intracerebroventricular infusion of insulin-like growth factor-1 (1 µg/24 h) or vehicle, from 3 to 14 days after asphyxia. Asphyxia was associated with ventricular enlargement, and loss of frontal and parietal white matter area (P < 0.05 versus sham-asphyxia). This was associated with reduced area fraction of myelin basic protein and numbers of oligodendrocyte transcription factor 2 and mature, anti-adenomatous polyposis coli-positive oligodendrocytes in periventricular white matter (P < 0.05), with persistent inflammation and caspase-3 activation (P < 0.05). Four of eight foetuses developed cystic lesions in temporal white matter. Prolonged infusion with insulin-like growth factor-1 restored frontal white matter area, improved numbers of oligodendrocyte transcription factor 2-positive and mature, anti-adenomatous polyposis coli-positive oligodendrocytes, with reduced astrogliosis and microgliosis after 35 days recovery (P < 0.05 versus asphyxia). One of four foetuses developed temporal cystic lesions. Functionally, insulin-like growth factor-1-treated foetuses had faster recovery of EEG power, but not spectral edge. Encouragingly, these findings show that delayed, prolonged, insulin-like growth factor-1 treatment can improve functional maturation of periventricular white matter after severe asphyxia in the very immature brain, at least in part by suppressing chronic neural inflammation.

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