Severe systemic hypoxemia exerts detrimental effects on the choroid plexus – cerebrospinal fluid system in rats.

Systemic hypoxemia can cause acute brain injury, however the mechanisms behind this injury are not clear. We aimed to explore the effects of systemic hypoxemia on the choroid plexus (CP) / cerebrospinal fluid (CSF) system in rats. Hypoxemia was caused by exposing SD rats to 8% O₂ in N₂. The number of dead cells in the CPs and ependymal layers were estimated, with or without inhibition of hypoxia-related cytokines. Concentrations of 32 hypoxia-related cytokines in the CSF and plasma were estimated. The number of macrophages in the CPs, and the concentrations of the CSF and plasma proteins were assessed. Transmission electron microscopy (TEM) was used to analyze CP ultrastructure. Data was analyzed by one-way ANOVA or by Student's t-test and presented as mean ± SD; p < 0.05 was considered statistically significant. There was a significant effect of the duration of hypoxemia on the viabilities of CP cells and the ependymal layers. TEM revealed changes in the CP cells’ ultrastructure that were suggestive of apoptotic cell death. The duration of hypoxemia exerted a significant effect on the protein concentration in the CSF, but not in plasma. There was a significant effect of hypoxemia duration on concentrations of 14 hypoxia-related cytokines in the CSF. Inhibitions of either erythropoietin, vascular endothelial growth factor or peripheral TNFα signaling caused detrimental effects, protective effects, and detrimental effects on the CP viability during hypoxemia, respectively. Number of macrophages in the CPs decreased significantly during hypoxemia; that effect was cancelled out by peripheral TNFα inhibition. This data indicated that hypoxemia caused detrimental effects on the CP/CSF system, which was largely modulated by hypoxia-related cytokines.