新生大鼠早产儿脑白质损伤的多模态磁共振成像评估及机制探讨

高啸天 张海默 张孝祖 王怡静 毕惠宁 于淼 李艳 王晓莉

中国当代儿科杂志 ›› 0

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中国当代儿科杂志 ›› 0 DOI: 10.7499/j.issn.1008-8830.2411071
论著·实验研究

新生大鼠早产儿脑白质损伤的多模态磁共振成像评估及机制探讨

  • 高啸天1 张海默1 张孝祖1 王怡静1 毕惠宁1 于淼1 李艳2 王晓莉1
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Multi-modal magnetic resonance imaging assessment and mechanism exploration of preterm white matter injury in neonatal rats

  • GAO Xiao-Tian, ZHANG Hai-Mo, ZHANG Xiao-Zu, WANG Yi-Jing, BI Hui-Ning, YU Miao, LI Yan, WANG Xiao-Li.
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摘要

目的 基于多模态磁共振成像(magnetic resonance imaging, MRI) 结合组织学评估新生大鼠早产儿脑白质损伤(preterm white matter injury, PWMI) 并探讨其机制。方法 将健康3 日龄Sprague-Dawley 新生大鼠随机分为假手术组与PWMI 组(各组n=12)。通过缺氧、缺血法建立新生大鼠PWMI 模型。采用激光散斑成像技术观察建模后不同时间点新生大鼠脑血氧饱和度及血流量变化,采用多模态MRI 观察脑白质损伤情况,苏木精-伊红染色观察损伤侧纹状体区形态学变化,免疫荧光染色检测少突胶质祖细胞的增殖及分化。结果 建模后0、6、12、24、72 h,PWMI 组损伤侧相对血流量和相对血氧饱和度均低于假手术组(P<0.05)。建模后24 h,PWMI 组损伤侧脑白质可见T2 加权成像呈高信号,相对表观扩散系数值、洛伦兹差分值均低于假手术组(P<0.001);PWMI 组神经细胞排列紊乱,EdU+PDGFR-α+细胞数高于假手术组(P<0.001)。建模后28 d,PWMI 组脑白质区相对各向异性分数值、EdU+Olig2+细胞数以及髓鞘碱性蛋白、神经丝蛋白200 荧光强度均低于假手术组(P<0.001)。结论 多模态MRI 可活体评估新生大鼠PWMI 模型早、远期PWMI 变化,为新生儿PWMI 诊疗提供影像学和病理学依据;缺氧缺血可抑制新生大鼠少突胶质细胞祖细胞的增殖与分化,导致PWMI。

Abstract

To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. Methods Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points postmodeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. Results At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU+PDGFR-α+ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU+Olig2+ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). Conclusions Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxiaischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.

关键词

早产儿脑白质损伤 / 多模态磁共振成像 / 少突胶质祖细胞 / 新生大鼠

Key words

Preterm white matter injury / Multimodal magnetic resonance imaging / Oligodendrocyte precursor cell / Neonatal rat

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高啸天 张海默 张孝祖 王怡静 毕惠宁 于淼 李艳 王晓莉. 新生大鼠早产儿脑白质损伤的多模态磁共振成像评估及机制探讨[J]. 中国当代儿科杂志. 0 https://doi.org/10.7499/j.issn.1008-8830.2411071
GAO Xiao-Tian, ZHANG Hai-Mo, ZHANG Xiao-Zu, WANG Yi-Jing, BI Hui-Ning, YU Miao, LI Yan, WANG Xiao-Li.. Multi-modal magnetic resonance imaging assessment and mechanism exploration of preterm white matter injury in neonatal rats[J]. Chinese Journal of Contemporary Pediatrics. 0 https://doi.org/10.7499/j.issn.1008-8830.2411071

基金

国家自然科学基金(82071888);山东省自然科学基金(ZR2024MH067);2019 年高等学校青创人才引育计划;潍坊市科学技术发展计划项目(2021GX058)

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