Neuronalinjury and roles of apoptosis and autophagy in a neonatal rat model of hypoxia-ischemia-induced periventricular leukomalacia

Qiao,Lin; Fu,Jianhua; Xue,Xindong; Shi,Yongyan; Yao,Li; Huang,Wanjie; Li,Jun; Zhang,Dan; Liu,Na; Tong,Xin; Du,Yanna; Pan,Yuqing

doi:10.3892/mmr.2018.8570

Neuronalinjury and roles of apoptosis and autophagy in a neonatal rat model of hypoxia-ischemia-induced periventricular leukomalacia

Authors:
- Lin Qiao
- Jianhua Fu
- Xindong Xue
- Yongyan Shi
- Li Yao
- Wanjie Huang
- Jun Li
- Dan Zhang
- Na Liu
- Xin Tong
- Yanna Du
- Yuqing Pan
View Affiliations

Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: February 7, 2018 https://doi.org/10.3892/mmr.2018.8570
Pages: 5940-5949
Copyright: © Qiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As research into periventricular leukomalacia (PVL) gradually increases, concerns are emerging about long‑term neuron injury. The present study aimed to investigate neuronal injury and the relevant alterations in apoptosis and autophagy in a PVL model established previously. A rat model of hypoxia‑ischemia‑induced PVL was established. In the model group, Sprague‑Dawley (SD) rats [postnatal day 3 (P3)] were subjected to right common carotid artery ligation followed by suturing and exposed to 6‑8% oxygen for 2 h; in the control group, SD rats (P3) were subjected to right common carotid artery dissection followed by suturing, without ligation and hypoxic exposure. At 1, 3, 7 and 14 days following modeling, brain tissue samples were collected and stained with hematoxylin and eosin. Cellular apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and the protein and mRNA expression alterations of neuronal nuclei (NeuN), caspase‑3 and Beclin 1 in the model group were detected by western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses. Compared with the control group, the protein and mRNA expression levels of NeuN (a marker of mature neurons) were markedly reduced, the number of positive cells was increased as detected by TUNEL, and the protein and mRNA expression levels of caspase‑3 and Beclin 1 were elevated in the model group. In the rat model of hypoxia‑ischemia‑induced PVL, oligodendrocyte injury and myelinization disorders were observed, in addition to neuron injury, a decrease in mature neurons and the co‑presence of apoptosis and autophagy. However, apoptosis and autophagy exist in different phases: Apoptosis is involved in neuron injury, while autophagy is likely to have a protective role.

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