Ma Rui-Fang, Xue Lu-Lu, Liu Jin-Xiang, Chen Li, Xiong Liu-Lin, Wang Ting-Hua, Liu Fei
Department of Anesthesiology, Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; School of Basic Medical Sciences, Kunming Medical University, Kunming 650000, Yunnan, China.
State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, China.
Brain Res. 2024 Jan 1;1822:148580. doi: 10.1016/j.brainres.2023.148580. Epub 2023 Sep 12.
This study aimed to observe changes of rats' brain infarction and blood vessels during neonatal hypoxic ischemic encephalopathy (NHIE) modeling by Transcranial Doppler Ultrasonography (TCD) so as to assess the feasibility of TCD in evaluating NHIE modeling.
Postnatal 7-days (d)-old Sprague Dawley (SD) rats were divided into the Sham group, hypoxic-ischemic (HI) group, and hypoxia (H) group. Rats in the HI group and H group were subjected to hypoxia-1 hour (h), 1.5 h and 2.5 h, respectively. Evaluation on brain lesion was made based on Zea-Longa scores, hematoxylin-eosin (HE) staining and Nissl staining. The brain infarction and blood vessels of rats were monitored and analyzed under TCD. Correlation analysis was applied to reveal the connection between hypoxic duration and infarct size detected by TCD or Nissl staining.
In H and HI modeling, longer duration of hypoxia was associated with higher Zea-Longa scores and more severe nerve damage. On the 1 d after modeling, necrosis was found in SD rats' brain indicated by HE and Nissl staining, which was aggravated as hypoxic duration prolonged. Alteration of brain structures and blood vessels of SD rats was displayed in Sham, HI and H rats under TCD. TCD images for coronal section revealed that brain infarct was detected at the cortex and there was marked cerebrovascular back-flow of HI rats regardless of hypoxic duration. On the 7 d after modeling, similar infarct was detected under TCD at the cortex of HI rats in hypoxia-1 h, 1.5 h and 2.5 h groups, whereas the morphological changes were deteriorated with longer hypoxic time. Correlation analysis revealed positive correlation of hypoxic duration with infarct size detected by histological detection and TCD.
TCD dynamically monitored cerebral infarction after NHIE modeling, which will be potentially served as a useful auxiliary method for future animal experimental modeling evaluation in the case of less animal sacrifice.
本研究旨在通过经颅多普勒超声（TCD）观察新生大鼠缺氧缺血性脑病（NHIE）建模过程中脑梗死及血管的变化，以评估TCD在评价NHIE建模中的可行性。
将出生7天的Sprague Dawley（SD）大鼠分为假手术组、缺氧缺血（HI）组和缺氧（H）组。HI组和H组大鼠分别缺氧1小时、1.5小时和2.5小时。基于Zea-Longa评分、苏木精-伊红（HE）染色和尼氏染色对脑损伤进行评估。在TCD下监测并分析大鼠的脑梗死和血管情况。采用相关性分析揭示缺氧持续时间与TCD或尼氏染色检测到的梗死面积之间的联系。
在H组和HI组建模中，缺氧持续时间越长，Zea-Longa评分越高，神经损伤越严重。建模后1天，HE和尼氏染色显示SD大鼠脑内出现坏死，随着缺氧持续时间延长，坏死加重。TCD显示假手术组、HI组和H组SD大鼠脑结构和血管的改变。冠状切面的TCD图像显示，无论缺氧持续时间如何，HI大鼠的皮层均检测到脑梗死，且存在明显的脑血管反流。建模后7天，在缺氧1小时、1.5小时和2.5小时组的HI大鼠皮层，TCD检测到类似梗死灶，且随着缺氧时间延长，形态学改变恶化。相关性分析显示，缺氧持续时间与组织学检测和TCD检测到的梗死面积呈正相关。
TCD可动态监测NHIE建模后脑梗死情况，在减少动物牺牲的情况下，有望成为未来动物实验建模评估的有用辅助方法。
