6-ketoprostaglandin-f1-alpha and Nervous-System-Diseases

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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Behavior, Animal; Blotting, Western; Brain; Brain Edema; Brain Injuries; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Exploratory Behavior; Head Injuries, Closed; Immunoenzyme Techniques; Indomethacin; Male; Mice; Nervous System Diseases; Psychomotor Performance; Recovery of Function; Substrate Specificity