Increased permeability of blood-brain barrier caused by inflammatory mediators is involved in high altitude cerebral edema

Studies have shown that inflammatory mediators can result in increased permeability of blood-brain barrier (BBB) and even cerebral edema, but there is no report on whether high altitude hypoxia exposure can increase the permeability of BBB. In this study, the levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha) endothelin (ET), nitric oxide (NO) superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) and glutathione-peroxidase GSH-PX in the brain, the permeability of BBB, brain water content, and histology and ultrastructure of the brain were detected. Our results showed the levels of TNF alpha, ET, NO, GSH and MDA, and SOD activity in the brain were increased in an altitude and exposure time dependent manner, which peaked after 9 days of exposure at 5000 m. Meanwhile, the permeability of BBB and brain water content was also elevated. Histology and ultrastructure detection showed lanthanum nitrate granules leaking from the vessels and distributing in the brain. Furthermore, the positive relationship was noted between the levels of TNF alpha, ET, NO, GSH and MDA, and SOD activity and brain water content. These results suggested TNF alpha, ET, NO, SOD, MDA and GSH played important roles in the increased permeability of BBB, which was involved in the high altitude cerebral edema.