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Cyclo-oxygenase-2 mediates hyperbaric oxygen preconditioning-induced neuroprotection in the mouse model of surgical brain injury. 2009

Vikram Jadhav, and Robert P Ostrowski, and Wenni Tong, and Brenden Matus, and Rachel Jesunathadas, and John H Zhang

OBJECTIVE We investigated the role of cyclo-oxygenase-2 (COX-2) in mechanisms of hyperbaric oxygen preconditioning (HBO-PC) in the mouse model of surgical brain injury (SBI). METHODS C57BL mice were administered 100% oxygen for 1 hour at 2.5 atmosphere absolute for 5 consecutive days and subjected to SBI. Neurological status and brain edema were evaluated at 24 hours and 72 hours after the brain insult. Fluorescent immunostaining and Western blotting were performed to study hypoxia-inducible factor-1alpha and COX-2, respectively. Two doses of COX-2 inhibitor, NS398 (3 mg/kg and 10 mg/kg) were used to verify the role of COX-2 signaling pathway in the mechanism of HBO-PC. RESULTS HBO-PC improved neurological status and decreased brain edema at 24 hours and 72 hours after SBI. HBO-PC by itself and SBI independently increased COX-2 levels by 2-fold and 4-fold, respectively. HBO-PC, however, reduced increase in hypoxia-inducible factor-1alpha and COX-2 expression after SBI. The HBO-PC-induced improvement in neurological status and brain edema was reversed by a suboptimal dose of the COX-2 inhibitor, NS398 (10 mg/kg intraperitoneally; 1/4th of dose shown to provide neuroprotection), which itself had no effect on investigated end points. CONCLUSIONS HBO-PC attenuates postoperative brain edema and improves neurological outcomes after SBI. The HBO-PC-induced neuroprotection is mediated through COX-2 signaling pathways.

UI MeSH Term Description Entries
D008297 Male Males
D009578 Nitrobenzenes BENZENE derivatives carrying nitro group substituents.
D001929 Brain Edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6) Brain Swelling,Cerebral Edema,Cytotoxic Brain Edema,Intracranial Edema,Vasogenic Cerebral Edema,Cerebral Edema, Cytotoxic,Cerebral Edema, Vasogenic,Cytotoxic Cerebral Edema,Vasogenic Brain Edema,Brain Edema, Cytotoxic,Brain Edema, Vasogenic,Brain Swellings,Cerebral Edemas, Vasogenic,Edema, Brain,Edema, Cerebral,Edema, Cytotoxic Brain,Edema, Cytotoxic Cerebral,Edema, Intracranial,Edema, Vasogenic Brain,Edema, Vasogenic Cerebral,Swelling, Brain
D001930 Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits. Brain Lacerations,Acute Brain Injuries,Brain Injuries, Acute,Brain Injuries, Focal,Focal Brain Injuries,Injuries, Acute Brain,Injuries, Brain,Acute Brain Injury,Brain Injury,Brain Injury, Acute,Brain Injury, Focal,Brain Laceration,Focal Brain Injury,Injuries, Focal Brain,Injury, Acute Brain,Injury, Brain,Injury, Focal Brain,Laceration, Brain,Lacerations, Brain
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006931 Hyperbaric Oxygenation The therapeutic intermittent administration of oxygen in a chamber at greater than sea-level atmospheric pressures (three atmospheres). It is considered effective treatment for air and gas embolisms, smoke inhalation, acute carbon monoxide poisoning, caisson disease, clostridial gangrene, etc. (From Segen, Dictionary of Modern Medicine, 1992). The list of treatment modalities includes stroke. Oxygenation, Hyperbaric,Hyperbaric Oxygen Therapy,Hyperbaric Oxygen Therapies,Hyperbaric Oxygenations,Oxygen Therapies, Hyperbaric,Oxygen Therapy, Hyperbaric,Oxygenations, Hyperbaric,Therapies, Hyperbaric Oxygen,Therapy, Hyperbaric Oxygen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D013514 Surgical Procedures, Operative Operations carried out for the correction of deformities and defects, repair of injuries, and diagnosis and cure of certain diseases. (Taber, 18th ed.). Surgical Procedures,Ghost Surgery,Operative Procedures,Operative Surgical Procedure,Operative Surgical Procedures,Procedure, Operative Surgical,Procedures, Operative Surgical,Surgery, Ghost,Surgical Procedure, Operative,Operative Procedure,Procedure, Operative,Procedure, Surgical,Procedures, Operative,Procedures, Surgical,Surgical Procedure

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