Rodent neonatal bilateral carotid artery occlusion with hypoxia mimics human hypoxic-ischemic injury

Rodent neonatal bilateral carotid artery occlusion with hypoxia mimics human hypoxic-ischemic injury
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DOI:
10.1038/jcbfm.2009.56
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发表时间:
2009-07-01
影响因子:
6.3
通讯作者:
Ashwal, Stephen
Ashwal, Stephen
中科院分区:
医学1区
文献类型:
--
作者:
Recker, Rebecca;Adami, Arash;Ashwal, Stephen

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我们报告了一种新的临床相关的 10 日龄幼鼠新生儿缺氧缺血性损伤模型。双侧颈动脉闭塞和 8% 缺氧(1 至 15 分钟,BCAO-H)是由不同程度的损伤(轻度、中度、重度)引起的,使用磁共振成像(包括 24 小时和 21/28 天的弥散加权和 T2 加权成像)对其进行量化。我们开发了基于磁共振成像的大鼠幼崽严重程度评分,并将 3D 缺血损伤体积/大鼠幼崽严重程度评分与组织学和行为测试进行了比较。 24小时时,17/27动物观察到缺氧缺血性损伤;长期生存率为81%。磁共振成像病变体积与缺氧持续时间无关,但与大鼠幼仔严重程度评分相关,该评分用于将动物分为轻度(n = 21)、中度(n = 6)和重度(n = 10)组,平均脑病变体积分别为0.9%、33.2%和56.3%。组织学证实病变位置和组织学评分与大鼠幼仔严重程度评分相关。我们还发现伤害严重程度与多种行为任务之间存在极好的相关性。 P10幼鼠的双侧颈动脉闭塞和缺氧是新生儿缺氧缺血性损伤的绝佳模型,因为它会诱导类似于足月婴儿的弥漫性全身损伤。该模型可以产生分级损伤严重程度,与人类新生儿相似,但缺氧持续时间的操作是不可预测的。脑血流与代谢杂志 (2009) 29, 1305-1316; doi:10.1038/jcbfm.2009.56; 2009 年 5 月 13 日在线发布
We report a new clinically relevant model of neonatal hypoxic-ischemic injury in a 10-day-old rat pup. Bilateral carotid artery occlusion and 8% hypoxia (1 to 15 mins, BCAO-H) was induced with varying degrees of injury (mild, moderate, severe), which was quantified using magnetic resonance imaging including diffusion-weighted and T2-weighted imaging at 24 h and 21/28 days. We developed a magnetic resonance imaging-based rat pup severity score and compared 3D ischemic injury volumes/rat pup severity score with histology and behavioral testing. At 24 h, hypoxic-ischemic injury was observed in 17/27 animals; long-term survival was 81%. Magnetic resonance imaging lesion volumes did not correlate with hypoxia duration but correlated with rat pup severity score, which was used to classify animals into mild (n = 21), moderate (n = 6), and severe (n = 10) groups with average brain lesion volumes of 0.9%, 33.2%, and 56.3%, respectively. Histology confirmed lesion location and histologic scoring correlated with the rat pup severity score. We also found excellent correlation between injury severity and multiple behavioral tasks. Bilateral carotid artery occlusion and hypoxia in the P10 rat pup is an excellent model of neonatal hypoxic-ischemic injury because it induces diffuse global injury similar to the term infant. This model can produce graded injury severity, similar to that seen in human neonates, but manipulation with hypoxia duration is unpredictable. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1305-1316; doi: 10.1038/jcbfm.2009.56; published online 13 May 2009