Brain hydroxyl radical generation in acute experimental head injury. 1993

E D Hall, and P K Andrus, and P A Yonkers
Central Nervous System Diseases Research, Upjohn Company, Kalamazoo, Michigan.

The time course and intensity of brain hydroxyl radical (.OH) generation were examined in male CF-1 mice during the first hour after moderate or severe concussive head injury. Hydroxyl radical production was measured using the salicylate trapping method in which the production of 2,3- and/or 2,5-dihydroxybenzoic acid (DHBA) in brain 15 min after salicylate administration was used as an index of .OH formation. In mice injured with a concussion of moderate severity as defined by the 1-h posttraumatic neurologic recovery (grip score), a 60% increase in 2,5-DHBA formation was observed by 1 min after injury compared with that observed in uninjured mice. The peak in DHBA formation occurred at 15 min after injury (+67.5%; p < 0.02, compared with uninjured). At 30 min, the increase in DHBA lost significance, indicating that the posttraumatic increase in brain .OH formation is a transient phenomenon. In severely injured mice, the peak increase in DHBA (both 2,3- and 2,5-) was observed at 30 min after injury, but also fell off thereafter as with the moderate injury severity. Preinjury dosing of the mice with SKF-525A (50 mg/kg i.p.), an inhibitor of microsomal drug oxidations, did not blunt the posttraumatic increase in salicylate-derived 2,5-DHBA, thus showing that it is not due to increased metabolic hydroxylation. Neither injury nor SKF-525A administration affected the DHBA plasma levels. However, saline perfusion of the injured mice to remove the intravascular blood before brain removal eliminated the injury-induced increase in 2,5-DHBA, but did not affect the baseline levels seen in uninjured mice.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D011281 Pregnatrienes Pregnane derivatives containing three double bonds in the ring structures.
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D005841 Gentisates Salts and esters of gentisic acid. 2,5-Dihydroxybenzoic Acids,2,5 Dihydroxybenzoic Acids,Acids, 2,5-Dihydroxybenzoic
D006259 Craniocerebral Trauma Traumatic injuries involving the cranium and intracranial structures (i.e., BRAIN; CRANIAL NERVES; MENINGES; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. Frontal Region Trauma,Head Injuries,Head Trauma,Occipital Region Trauma,Parietal Region Trauma,Temporal Region Trauma,Craniocerebral Injuries,Crushing Skull Injury,Forehead Trauma,Head Injuries, Multiple,Head Injury, Minor,Head Injury, Open,Head Injury, Superficial,Injuries, Craniocerebral,Injuries, Head,Multiple Head Injuries,Occipital Trauma,Open Head Injury,Superficial Head Injury,Trauma, Head,Craniocerebral Injury,Craniocerebral Traumas,Crushing Skull Injuries,Forehead Traumas,Frontal Region Traumas,Head Injuries, Minor,Head Injuries, Open,Head Injuries, Superficial,Head Injury,Head Injury, Multiple,Head Traumas,Injuries, Minor Head,Injuries, Multiple Head,Injuries, Open Head,Injuries, Superficial Head,Injury, Craniocerebral,Injury, Head,Injury, Minor Head,Injury, Multiple Head,Injury, Open Head,Injury, Superficial Head,Minor Head Injuries,Minor Head Injury,Multiple Head Injury,Occipital Region Traumas,Occipital Traumas,Open Head Injuries,Parietal Region Traumas,Region Trauma, Frontal,Region Trauma, Occipital,Region Trauma, Parietal,Region Traumas, Frontal,Region Traumas, Occipital,Region Traumas, Parietal,Skull Injuries, Crushing,Skull Injury, Crushing,Superficial Head Injuries,Temporal Region Traumas,Trauma, Craniocerebral,Trauma, Forehead,Trauma, Frontal Region,Trauma, Occipital,Trauma, Occipital Region,Trauma, Parietal Region,Trauma, Temporal Region,Traumas, Craniocerebral,Traumas, Forehead,Traumas, Frontal Region,Traumas, Head,Traumas, Occipital,Traumas, Occipital Region,Traumas, Parietal Region,Traumas, Temporal Region
D006878 Hydroxides Inorganic compounds that contain the OH- group.
D000208 Acute Disease Disease having a short and relatively severe course. Acute Diseases,Disease, Acute,Diseases, Acute
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

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