title: Effects of selective and non-selective cyclooxygenase inhibition against neurological deficit and brain oedema following closed head injury in mice.
abstract: The implication of cyclooxygenase (COX) type 2 in post-traumatic consequences is so far controversial. In experimental models of traumatic brain injury (TBI), genetic disruption or pharmacological inhibition of COX-2 has been shown to be neuroprotective, deleterious or without effect. Therefore, the aim of our study was to investigate the effect of COX-2 inhibition against neurological deficit and brain oedema after TBI that was induced by mechanical percussion in male Swiss mice. Despite the increased level and activity of COX-2, its inhibition either with nimesulide (12 mg/kg) or meloxicam (2mg/kg) modified neither the neurological score nor the brain water content that were evaluated at 6 and 24h after injury. Interestingly, the non-selective COX inhibition with indomethacin (5mg/kg) significantly promoted neurological recovery at 6 and 24h after trauma, without improving brain oedema. In conclusion, the present study yields considerable evidence that COX-2 may not solely constitute an interesting target for the treatment of TBI consequences. Our data point to a potentially deleterious role of COX-1 in the development of neurological impairment in brain-injured mice. However, the neuroprotective mechanism of indomethacin remains to be clarified.
authors.affiliation: Laboratoire de Pharmacologie de la Circulation Cérébrale (EA 4475), Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: Haymen
authors.initials: H
authors.lastname: Girgis
authors.forename: Bruno
authors.initials: B
authors.lastname: Palmier
authors.forename: Nicole
authors.initials: N
authors.lastname: Croci
authors.forename: Mathieu
authors.initials: M
authors.lastname: Soustrat
authors.forename: Michel
authors.initials: M
authors.lastname: Plotkine
authors.forename: Catherine
authors.initials: C
authors.lastname: Marchand-Leroux
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000502:physiology; D016489:Head Injuries, Closed / Q000150:complications* / Q000188:drug therapy* / Q000201:enzymology; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology; D020127:Recovery of Function; D013379:Substrate Specificity
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; D007213:Indomethacin