Agematsu Kota, Korotcova Ludmila, Scafidi Joseph, Gallo Vittorio, Jonas Richard A, Ishibashi Nobuyuki
1] Department of Cardiac Surgery, Children's National Medical Center, Washington, DC [2] Center for Neuroscience Research, Children's National Medical Center, Washington, DC.
Center for Neuroscience Research, Children's National Medical Center, Washington, DC.
Pediatr Res. 2014 May;75(5):618-25. doi: 10.1038/pr.2014.9. Epub 2014 Jan 31.
White matter (WM) injury is common after cardiopulmonary bypass or deep hypothermic circulatory arrest in neonates who have cerebral immaturity secondary to in utero hypoxia. The mechanism remains unknown. We investigated effects of preoperative hypoxia on deep hypothermic circulatory arrest-induced WM injury using a combined experimental paradigm in rodents.
Mice were exposed to hypoxia (prehypoxia). Oxygen-glucose deprivation was performed under three temperatures to simulate brain conditions of deep hypothermic circulatory arrest including ischemia-reperfusion/reoxygenation under hypothermia.
WM injury in prenormoxia was identified after 35 °C-oxygen-glucose deprivation. In prehypoxia, injury was displayed in all groups. Among oligodendrocyte stages, the preoligodendrocyte was the most susceptible, while the oligodendrocyte progenitor was resistant to insult. When effects of prehypoxia were assessed, injury of mature oligodendrocytes and oligodendrocyte progenitors in prehypoxia significantly increased as compared with prenormoxia, indicating that mature oligodendrocytes and progenitors that had developed under hypoxia had greater vulnerability. Conversely, damage of oligodendrocyte progenitors in prehypoxia were not identified after 15 °C-oxygen-glucose deprivation, suggesting that susceptible oligodendrocytes exposed to hypoxia are protected by deep hypothermia.
Developmental alterations due to hypoxia result in an increased WM susceptibility to injury. Promoting WM regeneration by oligodendrocyte progenitors after earlier surgery using deep hypothermia is the most promising approach for successful WM development in congenital heart disease patients.
在因宫内缺氧导致脑发育不成熟的新生儿中，体外循环或深低温停循环后白质（WM）损伤很常见。其机制仍不清楚。我们使用啮齿动物的联合实验范式研究术前缺氧对深低温停循环诱导的WM损伤的影响。
将小鼠暴露于缺氧环境（术前缺氧）。在三种温度下进行氧糖剥夺，以模拟深低温停循环时的脑部状况，包括低温下的缺血再灌注/复氧。
在35℃氧糖剥夺后，在术前常氧状态下发现了WM损伤。在术前缺氧状态下，所有组均出现损伤。在少突胶质细胞各阶段中，前少突胶质细胞最易受损，而少突胶质细胞前体细胞对损伤有抗性。在评估术前缺氧的影响时，与术前常氧相比，术前缺氧状态下成熟少突胶质细胞和少突胶质细胞前体细胞的损伤显著增加，这表明在缺氧条件下发育的成熟少突胶质细胞和前体细胞具有更大的脆弱性。相反，在15℃氧糖剥夺后，术前缺氧状态下少突胶质细胞前体细胞未发现损伤，这表明暴露于缺氧环境的易感少突胶质细胞受到深低温的保护。
缺氧导致的发育改变使WM对损伤的易感性增加。对于先天性心脏病患者，在早期手术中使用深低温促进少突胶质细胞前体细胞的WM再生是成功实现WM发育最有前景的方法。
