Affiliations: Department of Pharmaceutical Biosciences, Uppsala
Biomedical Centre, Uppsala University, SE-751 24 Uppsala, Sweden | Department of Neuroscience, Neurosurgery, Uppsala
University Hospital, SE-751 85 Uppsala, Sweden
Note: [] Address for correspondence: Ernst Oliw, Department of
Pharmaceutical Biosciences, Uppsala Biomedical Centre, Uppsala University, P.O.
Box 591, SE-751 24 Uppsala, Sweden. Tel.: +46 18 471 4455; Fax: +46 18 55 29
36; E-mail: ernst.oliw@farmbio.uu.se
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.
