title: Effect of leukotriene inhibitors on evolution of experimental brain contusions.
abstract: OBJECTIVE
  Leukotriene levels increase in cerebrospinal fluid (CSF) following controlled cortical impact (CCI) injury in rats. We investigated the impact of two different leukotriene inhibitors in the CCI model on CSF leukotriene levels, brain water content (BWC), brain swelling (BS) contusion size and cellular response.
  
  
  METHODS
  134 male Sprague Dawley rats were investigated at 4, 24 and 72 h after CCI for CSF leukotriene levels and BWC/BS, lesion size in T2-weighted magnetic resonance imaging and immunohistochemistry. Animals received vehicle, MK-886, an inhibitor of 5-lipoxygenase activating protein, or Boscari(®) , a mixture of boswellic acids, acting as competitive nonredox 5-lipoxygenase inhibitors before trauma and then every 8 h until sacrifice.
  
  
  RESULTS
  The intracranial pressure (ICP) was unaffected by treatment. Boscari treatment reduced CSF leukotriene C4 increase by -45% at 4 h (P < 0.03) and increase of BWC and BS by 49% (P < 0.05) and -58% at 24 h. Treatment with both substances showed a reduction of lesion volume at 72 h by -21% (P < 0.01) in T(2) -weighted magnetic resonance imaging, which was reflected in a smaller lesion area determined from a NeuN labelled section (-17% to -20%, P < 0.05). Triple immunofluorescence and Fluoro-Jade B staining showed rarefaction of neurones, glia and vasculature in the contusion core, whereas in the pericontusional zone astro- and microglia were upregulated in the presence of dying neurones. Treatment resulted in an improved survival of NeuN labelled neurones in the pericontusional cortex (+15% to +20%, P < 0.05).
  
  
  CONCLUSIONS
  Leukotriene inhibition should be further investigated as therapeutic option to counteract secondary growth of traumatic brain contusions and to possibly improve pericontusional neuronal survival.
authors.affiliation: Department of Neurosurgery, University Hospital of Leipzig, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Voigt
authors.forename: C K
authors.initials: CK
authors.lastname: Donat
authors.forename: W
authors.initials: W
authors.lastname: Hartig
authors.forename: A
authors.initials: A
authors.lastname: Förschler
authors.forename: M
authors.initials: M
authors.lastname: Skardelly
authors.forename: D
authors.initials: D
authors.lastname: Stichtenoth
authors.forename: T
authors.initials: T
authors.lastname: Arendt
authors.forename: J
authors.initials: J
authors.lastname: Meixensberger
authors.forename: M U
authors.initials: MU
authors.lastname: Schuhmann
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D015289:Leukotrienes / Q000134:cerebrospinal fluid*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D002722:Chlorobenzenes
chemical_list: D007211:Indoles; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes