title: Effects of methylprednisolone and 4-chloro-3-hydroxyanthranilic acid in experimental spinal cord injury in the guinea pig appear to be mediated by different and potentially complementary mechanisms.
abstract: METHODS
  Blinded, placebo-controlled, parallel treatment group studies of the effects of methylprednisolone (MP) or 4-chloro-3-hydroxyanthranilate (4-Cl-3-HAA) on behavioral outcome and quinolinic acid tissue levels from experimental thoracic spinal cord injury in adult guinea pigs.
  
  
  OBJECTIVE
  To compare the effects of treatment with high-dose MP, a corticosteroid, and 4-Cl-3-HAA, a compound that inhibits synthesis of the neurotoxin quinolinic acid (QUIN) by activated macrophages. To explore the effect of different times of treatment using these two approaches to ameliorating secondary tissue damage.
  
  
  METHODS
  Laboratory animal studies at the University of North Carolina, Chapel Hill, NC, USA.
  
  
  METHODS
  Standardized spinal cord injuries were produced in anesthetized guinea pigs, using lateral compression of the spinal cord. Behavioral impairment and recovery were measured by placing and toe-spread responses (motor function), cutaneus trunci muscle reflex receptive field areas and somatosensory-evoked potentials (sensory function). Tissue quinolinic acid levels were measured by gas chromatograph/mass spectrometry.
  
  
  RESULTS
  The current experiments showed a reduction in delayed loss of motor and sensory function in the guinea pig with MP (150 mg kg(-1), intraperitoneally in split doses between 0.5 and 6 h), but no significant reduction in tissue QUIN. Improved sensory function was seen with a single dose of 60 mg kg(-1) MP intraperitoneally at 5 h after injury, but not at 10 h after injury. A single dose of 4-Cl-3-HAA at 5 h in the guinea pig did not produce the sensory and motor improvements seen in previous studies with 12 days of dosing, beginning at 5 h.
  
  
  CONCLUSIONS
  These studies, together with earlier findings, indicate that both drugs can attenuate secondary pathologic damage after SCI, but through separate mechanisms. These are most likely an acute reduction by MP of oxidative processes and reduction by 4-Cl-3-HAA of QUIN synthesis.
authors.affiliation: 1] Curriculum in Neurobiology and Division of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Acorda Therapeutics Inc., Ardsley, NY, USA [3] Department of Psychology, Ohio Wesleyan University, Delaware, OH, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Curriculum in Neurobiology and Division of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Gay
authors.affiliation: Laboratory of Neurotoxicology, National Institute of Mental Health, Chapel Hill, NC, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Heyes
authors.affiliation: 1] Curriculum in Neurobiology and Division of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Acorda Therapeutics Inc., Ardsley, NY, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Blight
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006168:Guinea Pigs; D008775:Methylprednisolone / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015095:3-Hydroxyanthranilic Acid; C026381:4-chloro-3-hydroxyanthranilic acid; D017378:Quinolinic Acid; D008775:Methylprednisolone