HSP-70-mediated hyperbaric oxygen reduces brain and pulmonary edema and cognitive deficits in rats in a simulated high-altitude exposure

Abstract

High-mountain sickness is characterized by brain and pulmonary edema and cognitive deficits. The definition can be fulfilled by a rat model of high-altitude exposure (HAE) used in the present study. This study aimed to investigate the protective effect of hyperbaric oxygen therapy (HBO 2 T) and to determine the underlying mechanisms. Rats were subjected to an HAE (9.7% O 2 at 0.47 absolute atmosphere of 6,000 m for 3 days). Immediately after termination of HAE, rats were treated with HBO 2 T (100% O 2 at 2.0 absolute atmosphere for 1 hour per day for 5 consecutive days) or non-HBO 2 T (21% O 2 at 1.0 absolute atmosphere for 1 hour per day for 5 consecutive days). As compared to non-HAE+non-HBO 2 T controls, the HAE+non-HBO 2 T rats exhibited brain edema and resulted in cognitive deficits, reduced food and water consumption, body weight loss, increased cerebral inflammation and oxidative stress, and pulmonary edema. HBO 2 T increased expression of both hippocampus and lung heat shock protein (HSP-70) and also reversed the HAE-induced brain and pulmonary edema, cognitive deficits, reduced food and water consumption, body weight loss, and brain inflammation and oxidative stress. Decreasing the overexpression of HSP-70 in both hippocampus and lung tissues with HSP-70 antibodies significantly attenuated the beneficial effects exerted by HBO 2 T in HAE rats. Our data provide in vivo evidence that HBO 2 T works on a remodeling of brain/lung to exert a protective effect against simulated high-mountain sickness via enhancing HSP-70 expression in HAE rats.