4.1.2. Brain injury
Nervous system tissues are the least tolerant to hypoxia among all tissues of the human body. The normal adult brain is very sensitive to hypoxia, as its weight is approximately 2% of the body weight; however, its oxygen consumption is only 20% of the total body oxygen consumption. High-altitude hypoxia, particularly acute hypoxia, causes central nervous system dysfunction. This can lead to high-altitude headaches, acute mountain sickness, high-altitude cerebral edema, and other brain injuries.
To date, 41 of the 57 enzymes have been identified in different brain regions (Kuban et al., 2021) . Due to the presence of different cell types with different needs and functions, the expression of CYPs in the brain is heterogeneous, and some enzymes are present at higher levels in specific neurons than in their counterparts in hepatocytes. An increasing number of studies have reported changes in the expression of CYPs in the brain during hypoxia. Hypoxia causes a substantial decrease in CYP19a1b activity and CYP19a1 mRNA and protein expression in the hypothalamus of the Atlantic croaker (Rahman et al., 2021). In vitro, Jacob et al. exposed the human brain microvascular endothelial cell line hCMEC/D3 to hypoxic conditions for 6 h and found that hypoxia reduced CYP1A1 and CYP1B1 expression (Jacob et al., 2015). Changes in CYP expression in the brain under hypoxia also lead to changes in endogenous metabolites, which, in turn, are involved in the hypoxic response of brain tissue. Liu et al. found that CYP2C11 and EET expression levels increased substantially after hypoxia. Hypoxic preconditioning (HPC) and EET reduced astrocyte death, whereas CYP-epoxygenase inhibition prevented HPC protection, suggesting that the CYP-epoxygenase pathway contributed to astrocyte tolerance to hypoxic injury (Liu et al, 2005). Changes in vascular tone during hypoxia regulate the cerebral blood flow to maintain the supply of oxygen and nutrients to the brain, and 20-HETE is a potent cerebral vasoconstrictor. Gebremedhin et al. found that hypoxia increased the open probability of K+Ca currents (NPo) and decreased the basal endogenous level of 20-HETE in the brain, and that exogenous 20-HETE attenuated hypoxia-induced activation of K+Cacurrents in rat brain arterial myocytes. After the inhibition of endogenous CYP4A activity, hypoxia did not potentiate the increase in the NPo of K+Cachannel currents, which may account for the hypoxia-induced activation of arterial K+Ca channel currents and cerebral vasodilation (Gebremedhin et al., 2008).