The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Behav Brain Res. 2021 Jul 9;409:113322. doi: 10.1016/j.bbr.2021.113322. Epub 2021 Apr 24.
Hypoxic ischemic (HI) brain injury is a significant cause of childhood neurological deficits. Preclinical rodent models are often used to study these deficits; however, no preclinical study has determined which behavioral tests are most appropriate for long-term follow up after neonatal HI.
HI brain injury was induced in postnatal day (PND) 10 rat pups using the Rice-Vannucci method of unilateral carotid artery ligation. Rats underwent long-term behavioral testing to assess motor and cognitive outcomes between PND11-50. Behavioral scores were transformed into Z-scores and combined to create composite behavioral scores.
HI rats showed a significant deficit in three out of eight behavioral tests: negative geotaxis analysis, the cylinder test and the novel object recognition test. These individual test outcomes were transformed into Z-scores and combined to create a composite Z-score. This composite z-score showed that HI rats had a significantly increased behavioral burden over the course of the experiment.
In this study we have identified tests that highlight specific cognitive and motor deficits in a rat model of neonatal HI. Due to the high variability in this model of neonatal HI brain injury, significant impairment is not always observed in individual behavioral tests, but by combining outcomes from these individual tests, long-term behavioral burden can be measured.
缺氧缺血性（HI）脑损伤是儿童神经功能缺陷的一个重要原因。临床前啮齿动物模型常用于研究这些缺陷；然而，没有临床前研究确定哪些行为测试最适合新生儿 HI 后的长期随访。
采用 Rice-Vannucci 法单侧颈总动脉结扎法诱导出生后第 10 天（PND）大鼠幼仔 HI 脑损伤。大鼠在 PND11-50 进行长期行为测试，以评估运动和认知结果。行为评分转换为 Z 评分并组合以创建综合行为评分。
HI 大鼠在八项行为测试中的三项中表现出明显的缺陷：负趋地性分析、圆筒测试和新物体识别测试。这些单项测试结果转换为 Z 评分并组合以创建综合 Z 评分。该综合 z 评分表明，HI 大鼠在实验过程中行为负担显著增加。
在这项研究中，我们已经确定了在新生 HI 大鼠模型中突出特定认知和运动缺陷的测试。由于新生儿 HI 脑损伤模型中的变异性很高，在个别行为测试中并不总是观察到明显的损伤，但通过结合这些单项测试的结果，可以测量长期的行为负担。
