Impact of chronic hypoxia on white matter and brain development in neonatal rat model
10.7507/1007-4848.201801064
- VernacularTitle:慢性缺氧对新生大鼠脑白质及脑发育的影响
- Author:
LIU Gang
1
,
2
;
SHI Bowen
1
,
2
;
HE Xiaomin
1
,
2
;
HUANG Junrong
3
,
4
;
CHEN Huiwen
1
,
2
;
ZHU Zhongqun
1
,
2
Author Information
1. Department of Cardiothoracic Surgery, Heart Center, Shanghai Children&rsquo
2. s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, P.R.China
3. Department of Cardiothoracic Surgery, Shenzhen Children'
4. s Hospital, Shenzhen, 518038, P.R.China
- Publication Type:Journal Article
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2018;25(11):986-992
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the impact of chronic hypoxia on white matter (WM) injury and brain development delay using a neonatal rat model, and to explore its value in simulating chronic hypoxic brain damage in cyanotic congenital heart disease (CHD). Methods Three-day-old Sprague-Dawley (SD) rats were randomly distributed to an experiment group (n=36, FiO2 10.5%±1.0%) and a control group (n=36, FiO2 21.0%±0.0%) and were raised for 12 days. (1) Body weight of SD rats was recorded every day and fresh brain weight was measured on P14. (2) H&E staining was performed on sections of brain tissue to observe pathological changes and ventricular size. (3) Immunohistochemistry (IHC) was applied to reveal alterations of oligodendroglial progenitor cells (OPC), preoligodendrocytes (PreOL) and myelin basic protein (MBP) in brain WM area. (4) Protein was extracted from 50 mg of brain tissue in WM area and expression of MBP was determined using Western blotting. (5) Motor function and coordination of rats (P30) were assessed via rotation experiment. Results (1) Body weight and brain weight were significantly less in the experiment group compared with the control group on P14 (body weight 14.92±1.26 gvs. 30.26±1.81 g, t=7.51, P<0.01; brain weight 0.68± 0.05 gvs.0.97±0.04 g, t=13.26, P<0.01); (2) HE staining: Sections of brain tissue from the experiment group showed ventricular size enlargement with a statistical difference (P<0.01), disordered cell organization, local neuronal death and leukomalacia. (3) The number of OPC and PreOL in the experiment group were significantly less than those in the control group (64.8±6.3vs. 126.2±8.4, t=11.19, P<0.01; 19.1±7.6vs. 46.7±9.5, t=7.28, P<0.01, respectively). MBP distribution was sparse and disorganized in the experiment group. (4) Western blotting: Expression of MBP was less in the experiment group (P<0.01). (5) Behavioral test: Time on rotarod was less in the experiment group with a statistical difference (P<0.01). Conclusion Chronic hypoxia can result in WM injury and brain development delay in neonatal rats, with features comparable to those seen in infants with cyanotic CHD.
