gms | German Medical Science

Objective: The focal component of traumatic brain injury (TBI) in humans can be mimicked by controlled cortical impact (CCI) injury of cortical areas in the forebrain of adult rats. We use this animal model to investigate the behaviour of cyclooxygenase 2-immunoreactivity (COX-2-ir) and the detection of macrophages and microglia following trauma.

Methods: This study was performed with paraformaldehyde-fixed frozen coronal forebrain sections from 50 rats perfused 24 or 72 hours following CCI (5 mm Impactor, 4 m/s, 200ms indentation time) including 9 controls, which were sham operated. Series of sections were applied to immunoperoxidase labelling of COX-2, CD68 (ED-1), Ox-42, and lectin-histochemical staining with tomatoe lectin. Multiple carbocyanine labelling of selected sections included neuronal, glial and vascular markers and were visualized by confocal laser-scanning microscopy with a LSM 510 Meta (Zeiss).

Results: Neuronal COX-2-ir was found in the hippocampus and in a small portion of neocortical cells in control rats. 24h after CCI, robust neuronal COX-2-staining was observed in the contusion site and its close vicinity, which continued to exist at 72h. Selective staining of macrophages with anti-CD68 appeared absent in controls and was up-regulated at 72, but not at 24h following CCI. Ox-42 staining and lectin-histochemistry showed an upregulation of microglia already at 24h. Immunofluorescence labelling revealed COX-2 and CD68-ir in overlapping brain regions, suggesting COX-2 activity in inflammatory cells as well.

Conclusions: Early up-regulation of COX-2-ir in neurons with strong persistence, simultaneous activation of microglia and late infiltration by macrophages were found to be histological hallmarks following brain contusions. The role of COX-2 and its products (prostaglandins) in posttraumatic contusion growth and in the development of neurological sequelae needs further evaluation, since first experiments with COX-2 inhibitors have suggested a neuroprotective effect. This is of special importance, since leukotriene inhibition, which is the alternative pathway of arachidonic acid metabolism, seems to attenuate growth of brain contusion as well.