3D doppler ultrasound imaging of cerebral blood flow for assessment of neonatal hypoxic-ischemic brain injury in mice.
3D doppler ultrasound imaging of cerebral blood flow for assessment of neonatal hypoxic-ischemic brain injury in mice.
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DOI：
10.1371/journal.pone.0285434
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Ma, Qingyi
中科院分区：
文献类型：
--
作者：
Shen, Guofang;Sanchez, Kayla;Hu, Shirley;Zhao, Zhen;Zhang, Lubo;Ma, Qingyi
新生儿缺氧缺血性脑病（HIE）的脑血流量（CBF）急剧减少。临床研究表明，严重的 CBF 损伤可以预测新生儿的 HIE 结局。在此，本研究采用非侵入性3D超声成像方法来评估HI损伤后CBF的变化，并探讨CBF变化与HI诱发的小鼠脑梗塞之间的相关性。使用 Rice-Vannucci 模型在出生后第 7 天的小鼠幼崽中诱导新生儿 HI 脑损伤。在颈总动脉 (CCA) 结扎前、结扎后立即以及 HI 后 0 或 24 小时对小鼠幼仔进行非侵入性 3D 超声成像，以多个频率对 CBF 变化进行成像。单侧CCA结扎或联合缺氧后，同侧半球的血管比率急剧降低，并在HI后24小时部分恢复。此外，回归分析显示，HI后24小时同侧半球的血管分布比与脑梗死面积呈中度相关，表明CBF减少有助于HI脑损伤。为了进一步验证 CBF 与 HI 诱导的脑损伤之间的关联，在 HI 损伤一小时后，将神经肽 C 型利尿钠肽 (CNP) 或 PBS 鼻内施用到小鼠幼崽的大脑中。进行了脑梗塞、CBF 成像和长期神经行为测试。结果表明，鼻内给予CNP可保留HI脑损伤后的同侧CBF，缩小梗塞面积，改善神经功能。我们的研究结果表明，CBF 改变是新生儿 HI 脑损伤的一个指标，而 3D 超声成像是评估小鼠模型中 HI 脑损伤的一种有用的非侵入性方法。
Cerebral blood flow (CBF) acutely reduces in neonatal hypoxic-ischemic encephalopathy (HIE). Clinic studies have reported that severe CBF impairment can predict HIE outcomes in neonates. Herein, the present study uses a non-invasive 3D ultrasound imaging approach to evaluate the changes of CBF after HI insult, and explores the correlation between CBF alterations and HI-induced brain infarct in mouse pups. The neonatal HI brain injury was induced in postnatal day 7 mouse pups using the Rice-Vannucci model. Non-invasive 3D ultrasound imaging was conducted to image CBF changes with multiple frequencies on mouse pups before common carotid artery (CCA) ligation, immediately after ligation, and 0 or 24 hours after HI. Vascularity ratio of the ipsilateral hemisphere was acutely reduced after unilateral ligation of the CCA alone or in combination with hypoxia, and partially restored at 24 hours after HI. Moreover, regression analysis showed that the vascularity ratio of ipsilateral hemisphere was moderately correlated with brain infarct size 24 hours after HI, indicating that CBF reduction contributes to of HI brain injury. To further verify the association between CBF and HI-induced brain injury, a neuropeptide C-type natriuretic peptide (CNP) or PBS was intranasally administrated to the brain of mouse pups one hour after HI insult. Brain infarction, CBF imaging and long-term neurobehavioral tests were conducted. The result showed that intranasal administration of CNP preserved ipsilateral CBF, reduced the infarct size, and improved neurological function after HI brain injury. Our findings suggest that CBF alteration is an indicator for neonatal HI brain injury, and 3D ultrasound imaging is a useful non-invasive approach for assessment of HI brain injury in mouse model.
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