Establishment of Hypoxic-ischemic Encephalopathy Model in Full-term Infants
Objective To establish a simple and stable rat model of full-term infants with the whole hypoxic-ischemic brain damage(HIBD)in full-term infants and to explore the evaluation method of the model.Method Eighty-two 10-day-old SD rats were randomly divided into sham operation group(Sham,n=22)and model group(HIBD,n=60).The whole brain HIBD rat model of full-term infants was prepared by ligating the bilateral common carotid arteries of 10-day-old SD rats for 1.5 hours and revascularization after 30 minutes of hypoxia.The sham operation group did not receive ischemia and hypoxia treatment.(1)Pathological related detection:3 days after operation,TTC staining,HE and Nissl staining,hippocampal electron microscopy were used to observe the pathological changes of brain tissue.Brain water content was measured by brain dry-wet ratio method to evaluate brain edema.(2)Behavioral evaluation:Convulsion assessment was performed 12 hours after surgery,Longa score was performed 3 days after surgery,suspension test was performed 10 days after surgery,and Morris water maze test was performed 3 weeks after surgery.HIBD was graded according to the postoperative general condition and behavioral experiment result.Result Compared with the sham operation group,TTC staining showed bilateral white infarcts in the HIBD group.HE and Nissl staining showed disordered arrangement and necrosis of neurons in hippocampus.Electron microscopy showed neuronal cell edema,mitochondrial vacuolization,and increased autophagic lysosomes in the hippocampus.Brain water content increased significantly(P<0.01).Compared with the sham operation group,rats in the HIBD group had seizures with different degrees of motor nerve dysfunction in the early stage,and developmental delay and decreased learning and cognitive ability in the long term(P<0.01).Conclusion The pathological model of moderate to severe neonatal rat HIBD can be reproduced by ligation of bilateral common carotid arteries,hypoxia and recanalization in 10-day-old neonatal rats.
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