Article
Leukotriene synthesis inhibitors attenuate posttraumatic lesion size, CSF leukotriene levels and pericontusional inflammatory reaction in a brain contusion model
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Published: | May 20, 2009 |
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Objective: To test the hypothesis that leukotrienes are involved in the process of increasing contusion size and brain edema development, we investigated the effect of MK-886, an inhibitor of 5-lipoxygenase (5-LO) synthesis and of Boscari, a competitive non-redox 5-LO inhibitor.
Methods: 92 SD rats were investigated at 24h and 72h after Controlled Cortical Impact injury. Controls received vehicle (Group C, n=32), treated animals MK-886 5mg/kg, (Group M, n=28) or Boscari 100 mg/kg,(Group B, n=28) 1h before trauma and every 8h thereafter. MRI scans (n=42) or ICP determination (n=50) was performed. Immunohistochemistry visualized neurones, astrocytes, microglia, neutrophils, macrophages and vessels. CSF leukotriene levels were determined. Lesion size was determined from T2 MRI scans and NeuN stained sections.
Results: ICP values were not raised in any group. Lesion volume in T2 images decreased in both treatment groups at 24h, with significant differences at 72h (p<0.02). Planimetry of NeuN stained brain slices also found a significant decrease of the lesion. Immunhistochemistry showed a significant decrease of CD-68 positive macrophages and CD-43 positive neutrophil granulocytes in the penumbra zone bordering the contusion at the peak of the inflammatory reaction at 72 hours in both treatments groups (p<0.01). Preceding the inflammatory peak, CSF cys-leukotriene levels were significantly decreased at 24h (p<0.05), however not at 72h.
Conclusions: The application of leukotriene synthesis inhibitors, does lead to an decrease of cys-leukotriene levels in the CSF at 24h. This is followed by a decrease of contusion size at 72h after trauma and by a decrease of the pericontusional inflammatory reaction. Thus, leukotriene synthesis inhibitors seem to be effective by attenuating the posttraumatic inflammatory reaction. This could be a result of a decrease of posttraumatic cys-leukotriene levels. However, a different mode of action cannot be excluded.