Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat.
OBJECTIVE
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 approximately 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.
Kunz
Tina
T
Department of Pharmaceutical Biosciences, Uppsala Biomedical Centre, Uppsala University, SE-751 24 Uppsala, Sweden.
Marklund
Niklas
N
Hillered
Lars
L
Oliw
Ernst H
EH
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005452:Fluoresceins; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009930:Organic Chemicals; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013450:Sulfones / Q000627:therapeutic use*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D005452:Fluoresceins; D007783:Lactones; D009930:Organic Chemicals; D013450:Sulfones; C435731:fluoro jade; C116926:rofecoxib