Effect Of Nimesulide Against Traumatic Brain Injury-induced Brain Edema, Myelopreoxidase And Matrix Metalloproteinase-2Changes In Rats

Object:The overproduction of reactive oxygen species and resultant damage to cellular proteins or lipids of cell membranes and DNA by free radicals are the underlying mechanisms of many neuropathologies. Cyclooxygenase-2(Cyclooxy genase-2, COX-2) inhibitors have been suggested to be neuroprotective by reducing prostanoid and free radical synthesis, or by directing arachidonic acid metabolism through alternate pathways. This study investigated the putative neuroprotective effect of the COX-2inhibitor, nimesulide, in a rat model of traumatic brain injury.Methods:Forty male Sprague-Dawley rats were divided four groups, which were control, nimesulide (6mg/kg, i.p.), trauma and trauma+nimesulide (6mg/kg, i.p.). Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using300g-1m weight-height impact. Twenty-four hours after the injury, neurological examination scores were measured, the animals were decapitated and brain tissues were taken. Brain edema and blood-brain barrier (BBB) permeability were evaluated by wet-dry weight method and Evans blue(EB) extravasation respectively. In brain tissue, myelopreoxidase and matrix metalloproteinase-2were measured and histopathological observation.Result:The neurological examination scores increased in trauma groups24hours after the induction of trauma. Nimesulide treatment improved the altered neurological status. In trauma group, water contents and EB contents were significantly higher than control group (P<0.05).In trauma+nimesulide group, water contents and EB contents were significantly lower than trauma group. In trauma+nimesulide group, the content of MPO protein and MMP-2protein were significantly lower than trauma group, the change of MPO protein were positively correlated with the change of the MMP-2protein.Conclusion:Nimesulide exerts neuroprotective effect by preserving BBB permeability and by inhibiting the overexpression of myelopreoxidase and metalloproteinase-2(probably by its anti-inflammatory properties) in the diffuse brain injury model.