Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat

Abstract

Purpose: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury.

Methods: Rofecoxib (n=23) or vehicle (n=20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay.

Results: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12–72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12–72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was ∼50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p=0.06), and appeared unchanged at 72 h.

Conclusions: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury.