Preconditioning With Hyperbaric Oxygen
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.
Spontaneous ICH, from a variety of sources, causes instantaneous mass effect, disruption of the surrounding brain, and often an early neurological death. In patients that survive the initial ictus, the question of whether to remove the hematoma often arises. The recently reported Surgical Trial in Intracerebral Hemorrhage (STICH) failed to show a benefit of early surgery compared with conservative medical therapy for ICH, and there is a great need for novel therapies.
The protective effect of ischemic preconditioning, in which a brief ischemic episode can increase tolerance to subsequent severe ischemia, occurs in the brain. Ischemic tolerance can be achieved not only by a brief period of global or focal ischemia, but also by a wide range of other preconditioning stimuli, including hypoxia, hyperthermia, cytokines, and intracerebral low-dose thrombin infusion. Recent studies have demonstrated that preconditioning with HBO2 can also reduce ischemic brain damage. It is not clear, however, whether or not such preconditioning can reduce brain injury after ICH.
The precise mechanisms involved in preconditioninginduced ischemic tolerance have not been fully determined. Many mechanisms, including improving the efficiency of energy metabolism, reducing excitotoxic injury, and limiting apoptosis, have been associated with ischemic tolerance. Activation of p44/42 MAPK, which are cytoplasmic signaling molecules, may be an important step in preconditioning- induced brain tolerance.
This study investigated whether or not preconditioning with HBO2 can induce tolerance to brain edema formation after ICH and the role of p44/42 MAPK in HBO2 preconditioning- induced protection.
Abstract and Introduction
Abstract
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.
Introduction
Spontaneous ICH, from a variety of sources, causes instantaneous mass effect, disruption of the surrounding brain, and often an early neurological death. In patients that survive the initial ictus, the question of whether to remove the hematoma often arises. The recently reported Surgical Trial in Intracerebral Hemorrhage (STICH) failed to show a benefit of early surgery compared with conservative medical therapy for ICH, and there is a great need for novel therapies.
The protective effect of ischemic preconditioning, in which a brief ischemic episode can increase tolerance to subsequent severe ischemia, occurs in the brain. Ischemic tolerance can be achieved not only by a brief period of global or focal ischemia, but also by a wide range of other preconditioning stimuli, including hypoxia, hyperthermia, cytokines, and intracerebral low-dose thrombin infusion. Recent studies have demonstrated that preconditioning with HBO2 can also reduce ischemic brain damage. It is not clear, however, whether or not such preconditioning can reduce brain injury after ICH.
The precise mechanisms involved in preconditioninginduced ischemic tolerance have not been fully determined. Many mechanisms, including improving the efficiency of energy metabolism, reducing excitotoxic injury, and limiting apoptosis, have been associated with ischemic tolerance. Activation of p44/42 MAPK, which are cytoplasmic signaling molecules, may be an important step in preconditioning- induced brain tolerance.
This study investigated whether or not preconditioning with HBO2 can induce tolerance to brain edema formation after ICH and the role of p44/42 MAPK in HBO2 preconditioning- induced protection.
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