Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit

作者：Zhang, Xinyang; Fu, Chen; Chen, Baoxin; Xu, Zhenmin; Zeng, Zixiu; He, Lijuan; Lu, Yan; Chen, Zhigang; Liu, Xuemei^*

来源：MEDICAL SCIENCE MONITOR, 2019, 25: 1373-1382.

DOI：10.12659/MSM.915123

• Autophagy
• Hypoxia-Ischemia
• Brain
• Stroke

Background: Autophagy is characterized by the degradation of cellular components in autophagosomes. It plays a significant role in cerebral ischemic injury and has a complex functional connection with apoptosis. The neurovascular unit (NVU) is a structural and functional unit of the nervous system presented as a therapeutic target of stroke. This study aimed to investigate the effect of autophagy induced by ischemic damage on NVUs.
Material/Methods: SH-SY5Y cells, C6 cells, and rat brain microvascular endothelial cells were cultured with oxygen-glucose deprivation (OGD) exposure for different time durations, and 3-methyladenine (3-MA) was added as an autophagy inhibitor. In all 3 cell lines, lactate dehydrogenase (LDH) release was measured. Furthermore, apoptosis was detected using Annexin V-fluorescein isothiocyanate/propidium iodide labeling and immunofluorescence staining. Autophagosomes were observed through AO/MDC (acridine orange/monodansycadaverine) double staining. LC3-II expression levels were evaluated by western blot analysis.
Results: In the OGD groups of 3 cell lines, LDH leakage, and apoptotic rates were obviously increased. Remarkable in- crease in LC3-II expression was found in the OGD groups of SH-SY5Y cells and C6 cells. However, 3-MA decreased the LC3-II expression to varying degrees.
Conclusions: OGD could induce the over-activation of autophagy and augment the apoptotic activity in neurons and glial cells of NVUs.

• 出版日期2019-2-21
• 单位北京中医药大学; 中国中医科学院西苑医院