Effects of Hypoxia on Cerebral Microvascular Angiogenesis: Benefits or Damages?

Cerebrovascular microcirculation is essential for maintaining the physiological functions of the brain. The brain can be protected from stress injury by remodeling the microcirculation network. Angiogenesis is a type of cerebral vascular remodeling. It is an effective approach to improve the blood flow of the cerebral microcirculation, which is necessary for preventing and treating various neurological disorders. Hypoxia is one of the most important regulators of angiogenesis, affecting the sprouting, proliferation, and maturation stages of angiogenesis. Moreover, hypoxia negatively affects cerebral vascular tissue by impairing the structural and functional integrity of the blood-brain barrier and vascular-nerve decoupling. Therefore, hypoxia has a dual effect on blood vessels and is affected by confounding factors including oxygen concentration, hypoxia duration, and hypoxia frequency and extent. Establishing an optimal model that promotes cerebral microvasculogenesis without causing vascular injury is essential. In this review, we first elaborate on the effects of hypoxia on blood vessels from two different perspectives: (1) the promotion of angiogenesis and (2) cerebral microcirculation damage. We further discuss the factors influencing the dual role of hypoxia and emphasize the benefits of moderate hypoxic irritation and its potential application as an easy, safe, and effective treatment for multiple nervous system disorders.