A new Hypoxic Ischemic Encephalopathy model in neonatal rats

Hao Lyu,Dong Ming Sun,Chi Ping Ng,Jun Fan Chen,Yu Zhong He,Sin Yu Lam,Zhi Yuan Zheng,Hadi Askarifirouzjaei,Chi Chiu Wang,Wise Young,Wai Sang Poon

doi:10.1016/j.heliyon.2021.e08646

Abstract

BackgroundHypoxic-Ischemic Encephalopathy (HIE) occurs when an infant's brain does not receive adequate blood and oxygen supply, resulting in ischemic and hypoxic brain damage during delivery. Currently, supportive care and hypothermia have been the standard treatment for HIE. However, there are still a 20% mortality and most of the survivors are associated with significant neurodevelopmental disability. HIE animal model was first established by Vannucci et al., in 1981, and has been used extensively to explore the mechanisms of brain damage and its potential treatment. The Vannucci model involves the unilateral common carotid artery occlusion followed by 90 min hypoxia (8% oxygen). The purpose of this study is to define and validate a modified HIE model which mimics closely that of the human neonatal HIE. MethodThe classic Vannucci HIE model occludes one common carotid artery followed by 90 min hypoxia. In the new model, common carotid arteries were occluded bilaterally followed by breathing 8% oxygen in a hypoxic chamber for 90, 60 and 30 min, followed by the release of the common carotid artery ligatures, mimicking a reperfusion. ResultWe studied 110 neonatal rats in detail, following the modified in comparison with the classical Vannucci models. The classical Vannucci model has a consistent surgical mortality of 18% and the new modified models have a 20%–46%. While mortality depended on the duration of hypoxia, fifty-two animals survived for behavioral assessments and standard histology. The modified HIE model with 60 min of transient carotid occlusion is associated with a moderate brain damage, and has a 30% surgical mortality. This modified experimental model is regarded closer to the human situation than the classical Vannucci model.

Highlights

Hypoxic-Ischemic Encephalopathy (HIE) is a leading cause of neonatal neurologic disabilities, including cerebral palsy, mental retardation, cognitive disorders and epilepsy
In 1981, Rice and co-workers developed the Vannucci HIE model that permanently ligates one common carotid artery followed by 8% hypoxia at 37 C for 3.5 h
A total of 110 unsexed rat pups were assigned to either unilateral carotid occlusion and 90 min of 8% hypoxia (Vannucci model, n 1⁄4 20) or to our bilateral carotid occlusion HIE model (n 90 minutes 1⁄4 13 and 35 for Day 1 and 5 study; n 60 minutes 1⁄4 22; n 30 minutes 1⁄4 20)

Summary

Introduction

Hypoxic-Ischemic Encephalopathy (HIE) is a leading cause of neonatal neurologic disabilities, including cerebral palsy, mental retardation, cognitive disorders and epilepsy. In 1981, Rice and co-workers developed the Vannucci HIE model that permanently ligates one common carotid artery followed by 8% hypoxia at 37 C for 3.5 h. This model caused moderate to severe brain damage at 50 h after the surgery (Hamdy et al, 2020; Rice et al, 1981). The modified HIE model with 60 min of transient carotid occlusion is associated with a moderate brain damage, and has a 30% surgical mortality. This modified experimental model is regarded closer to the human situation than the classical Vannucci model

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