Preconditioning with hyperbaric oxygen attenuates brain edema after experimental intracerebral hemorrhage

OBJECT: Preconditioning with hyperbaric oxygen (HBO2) reduces ischemic brain damage. Activation of p44/42 mitogen-activated protein kinases (p44/42 MAPK) has been associated with preconditioning-induced brain ischemic tolerance. This study investigated if preconditioning with HBO2 protects against intracerebral hemorrhage (ICH)-induced brain edema formation and examined the role of p44/42 MAPK in such protection. METHODS: The study had three experimental groups. In Group 1, Sprague-Dawley rats received two, three, or five consecutive sessions of preconditioning with HBO2 (3 ata, 100% oxygen, 1 hour daily). Twenty-four hours after preconditioning with HBO2, rats received an infusion of autologous blood into the caudate. They were killed 1 or 3 days later for brain edema measurement. Rats in Group 2 received either five sessions of preconditioning with HBO2 or control pretreatment and were killed 24 hours later for Western blot and immunohistochemical analyses. In Group 3, rats received an intracaudate injection of PD098059 (an inhibitor of p44/42 MAPK activation) before the first of five sessions of preconditioning with HBO2. Twenty-four hours after the final preconditioning with HBO2, rats received an intracaudate blood infusion. Brain water content was measured 24 hours after ICH. RESULTS: Fewer than five sessions of preconditioning with HBO2 did not significantly attenuate brain edema after ICH. Five sessions of preconditioning with HBO2 reduced perihematomal edema 24 and 72 hours after ICH (p < 0.05). Strong p44/42 MAPK immunoreactivity was detected in the basal ganglia 24 hours after preconditioning with HBO2. Intracaudate infusion of PD098059 abolished HBO2 preconditioning-induced protection against ICH-induced brain edema formation. CONCLUSIONS: Preconditioning with HBO2 protects against brain edema formation following ICH. Activation of the p44/42 MAPK pathway contributes to that protection. Preconditioning with HBO2 may be a way of limiting brain injury during invasive neurosurgical procedures that cause bleeding.