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).