Mild chronic hypoxia and the brain: an ambiguous relationship

Abstract Mild hypoxia is a common condition encountered in various situations, such as high-altitude living, respiratory diseases, anaemia, and certain cardiovascular disorders. At the same time, mild hypoxia often goes unnoticed and can lead to long-term brain impairments. Understanding the subtle effects of mild hypoxia on the brain is essential for early diagnosis and intervention to prevent serious neurological and psychiatric complications. The pathophysiology of mild chronic hypoxia is complex; nevertheless, based on the literature, two main pathways can be distinguished. The first involves the direct effects of mild hypoxia on the brain and spinal cord, while the second involves the influence of enhanced systemic inflammation. In this narrative review, we discuss the current understanding of the effects of mild hypoxia on brain metabolism, cellular models, perfusion, the blood–brain barrier (BBB), the blood–spinal cord barrier (BSCB) and the brain-cerebrospinal fluid barrier (BCSFB). We explore the intricate relationship between peripheral inflammation induced by hypoxia and the BBB/BSCB/BCSFB, shedding light on the underlying mechanisms and their potential implications for central nervous system health. Graphical abstract