Himadri, P., S. K. S. Sarada, M. Chitharanjan, and S. Dhananjay. Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: a molecular approach. High Alt. Med. Biol. 11:231–244, 2010.—The present study reports the possible role of oxidative stress and inflammation (role of nuclear factor, NFκB) in hypoxia-induced transvascular leakage in brain of rats. The rats were exposed to a simulated altitude of 25,000 ft for different durations: 0, 3, 6, 12, 24, and 48 h. Brain water content, transvascular leakage, oxidative stress, and proinflammatory parameters were studied at different durations of hypoxic exposure. The results revealed that maximum increase in transvascular leakage in brain of rats was observed at 24 h of hypoxic exposure (240.16 ± 1.95 relative fluorescence unit (r.f.u)/g tissue) compared with control (100.58 ± 1.79 r.f.u/g tissue). There was a significant increase in reactive oxygen species (ROS) and lipid peroxidation (MDA), with concomitant reduction in antioxidants. Hypoxic exposure resulted in a significant increase in NFκB protein expression levels and in the DNA binding activity in the 24-h hypoxic exposure (p < 0.001) compared with control. There was a significant increase in proinflammatory cytokines, with concomitant upregulation of cell adhesion molecules. Simultaneously, to rule out the fact that inflammation causes cerebral edema, the rats were pretreated with curcumin (100 mg/kg body weight) 1 h prior to 24-h hypoxia. Curcumin pretreatment significantly attenuated the hypoxia-induced cerebral transvascular leakage (p < 0.05), with concomitant downregulation in the expression of brain NFκB levels (p < 0.001). The present study therefore reveals that inflammation (NFκB) plays a significant role in hypoxia-induced cerebral edema.
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