NB-3 expression in endothelial cells contributes to the maintenance of blood brain barrier integrity in a mouse high-altitude cerebral edema model.

Abstract

NB-3, a member of the contactin/F3 subgroup in the immunoglobulin superfamily, plays an important role in neural development and injury recovery. The blood brain barrier (BBB) is typically involved in the pathophysiology of neural disorders, such as hypoxic-ischemic brain injury. Our previous research found that NB-3 protects against brain damage in a mouse stroke model. However, its role in high-altitude disorders caused by hypobaric hypoxia exposure remains unknown. In the present study, we found that NB-3 was expressed in brain microvascular endothelial cells (BMECs) and responded to hypoxia stimulation. Conditional knockout of NB-3 in endothelial cells increased BBB leakage and downregulated tight junction proteins in vivo. NB-3 deficiency promoted the downregulation of tight junction proteins under Lipopolysaccharide (LPS)/hypoxia stimulation. Conversely, overexpression or supplementation with NB-3 alleviated endothelial barrier injuries. Transcriptome sequencing showed that NB-3 regulated various cell attachment genomic changes, including the Notch signaling pathway. Blocking the Notch signaling pathway increased VEGF/VEGFR2 pathway activation induced by LPS/hypoxia. Collectively, we present evidence that NB-3 plays key roles in maintaining BBB integrity under high-altitude cerebral edema conditions.

• Authors: Yanzhao Zhou, Feng Yan, Xue Han, Xin Huang, Xiang Cheng, Yanan Geng, Xiufang Jiang, Ying Han, Ming Zhao, Lingling Zhu
• Journal: Experimental neurology (Exp Neurol) Vol. 354 Pg. 114116 (08 2022) ISSN: 1090-2430 [Electronic] United States
• PMID: 35584741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Cell Adhesion Molecules, Neuronal
• Lipopolysaccharides
• Tight Junction Proteins
• contactin 6 protein, mouse

Topics

• Altitude
• Altitude Sickness
• Animals
• Blood-Brain Barrier (metabolism)
• Brain Edema (etiology, metabolism)
• Cell Adhesion Molecules, Neuronal (metabolism)
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Hypoxia (metabolism)
• Lipopolysaccharides
• Mice
• Tight Junction Proteins (metabolism)