Relationship between blood–brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport?

Abstract

The blood–brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood–brain barrier’s structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system’s function is drastically altered, which can cause disease and modify the metabolism of drugs in vivo. Changes in the structure and function of the blood–brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes. This article aims to review the effects of high-altitude hypoxia on the structure and function of the blood–brain barrier as well as the effects of changes in the blood-brain barrier on drug metabolism. We also hypothesized and explore the regulation and potential mechanisms of the blood-brain barrier and associated pathways, such as transcription factors, inflammatory factors, and nuclear receptors, in regulating drug transport under high-altitude hypoxia.

Keywords:

• Blood–brain barrier
• high-altitude hypoxia
• drug transporters
• drug-metabolizing enzymes
• drug transport

Acknowledgements

Figures 1–8 were created with BioRender.com with permission.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant No. 82260731; Qinghai Innovation Platform Construction Project under Grant No. 2021-ZJ-T03.