Effect of U74006F on neurologic function and brain edema after fluid percussion injury in rats. 1993

T Sanada, and T Nakamura, and M C Nishimura, and K Isayama, and L H Pitts
Department of Neurological Surgery, School of Medicine, University of California, San Francisco.

The effect of the 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on neurologic outcome and cerebral edema was evaluated in adult male Sprague-Dawley rats subjected to a fluid percussion temporal brain injury followed by 45 min of hypoxia (PaO2 = 30.0 mm Hg). The rats were divided randomly into five groups. Bolus injections of a control drug or U74006F (1.0, 3.0, 10.0, or 30.0 mg/kg) were given 3 min and 3 h after the injury. Twenty-four hours after the injury, the neurologic status was evaluated, the rats were killed, and brain water content was determined by microgravimetry. U74006F did not significantly reduce brain water content at any dose level, nor did it affect rotorod walking or activity scores. However, rats treated with U74006F at a dose of 10.0 mg/kg had significantly better motor function scores (p < 0.05) than rats in the control group. These findings demonstrate the usefulness of U74006F as a cerebroprotective agent in this model of experimental head injury.

UI MeSH Term Description Entries
D008054 Lipid Peroxides Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009420 Nervous System The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed) Nervous Systems,System, Nervous,Systems, Nervous
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D011281 Pregnatrienes Pregnane derivatives containing three double bonds in the ring structures.
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001834 Body Water Fluids composed mainly of water found within the body. Water, Body
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

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