Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Aims: Leukotriene levels increase in cerebrospinal fluid following controlled cortical impact (CCI) injury in rats. We investigated the impact of leukotrienes on contusion size by the effect of two different leukotriene inhibitors in the CCI model.

Methods: 92 male Sprague-Dawley rats were investigated at 24h and 72h after CCI with MRI (n= 40) and immunohistochemistry (n=52). Animals received vehicle or either MK886, an inhibitor of 5-lipoxygenase activating protein, or Boscari, a mixture of boswellic acids, acting as competitive non-redox 5-lipoxygenase inhibitors prior to trauma and then every 8 hours until sacrifice.

Results: Global ICP was within normal limits and unaffected by treatment. T2 weighted MRI showed a reduction of lesion volume in treatment groups at 72h by -21% (p<0.01), which was reflected in a smaller lesion area determined from a NeuN labelled section (-17% to -20%, p<0.05). Qualitative characterization by triple immunofluorescence and Fluorojade B staining showed progressive rarefaction of neurons, glia and vasculature in the contusion core, whereas in the pericontusional zone astro- and microglia were up-regulated in the presence of dying neurons. Treatment resulted in an improved survival of NeuN labelled neurons in the pericontusional cortex (+15% to +20%, p<0.05).

Conclusions: Two differently acting leukotriene inhibitors lead to an attenuation of lesion growth and improved pericontusional neuronal survival following CCI. Therefore, leukotrienes seem to be involved in brain contusion growth and pericontusional secondary injury. Leukotriene inhibition should be further investigated as therapeutic option to counteract secondary growth of traumatic brain contusions and to possibly improve pericontusional neuronal survival.