The Effects Of Ketamine On Nitric Oxide, Free Radical And Neurological Outcome After Cold-induced Injury

Objective: Excitatory amino acid (EAA) an important neurotransmitter is released in excessive amounts from terminals of postsynaptic on traumatic brain injury. These excessive levels of EAA initiate a cascade of events believed to lead to second delayed damage to central nervous system, in addition by NMDA receptor/NOS/cGMP pathway and free radical. The N-methyl-D-aspartate non-competitive receptor antagonist ketamine was reported to reduce the neurotoxic effects of EAA and to attenuate the development of second delayed injury. The present study was undertaken to examine the effects of treatment with ketamine on nitric oxide, free radical, and neurological outcome after cold-induced injury.Methods: Forty-nine Sprague-Dawley rats were divided into seven groups. Group A was surgically prepared but received no cold injury. Groups B, C, D and E, F, G received cold injury to the left cranium. But groups B, C and D received no treatment. Groups E, F and G received 180mg/kg IP ketamine 1 hour after head trauma, respectively. Neurological severity score (NSS) was determined at l,2,6and 24 hours after head trauma. After death at 2,6 and 24 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites in the contralateral hemisphere for determination of tissue NOS,MDA,SOD and water content.Results: NSS, NOS, MDA, NO and water content was Increased and SOD, number of neuron In hippocampus region was decreased after head trauma. Ketamine given in E, F and G group at 1 hour after trauma, reduced NOS levels from 2.33+0.66U/mgprot and 1.48+0.52U/mgprotat 2 hours to 3.29+0. 97U/mgprot and 2.19+0.54U/mgprot at 6 hours, respectively; reduced MDA from 19.41 + 2.58nmol/tngprot and 15.48 + 3.03nmol/mgprot at 2 hour to 22.39+3.25nmol/mgprot and 17.01 + 2.91nmol/mgprot at 6 hours, respectively; increased SOD from 110.37 + 14.3UN/mgprot and 130.40 + 17.53UN/mgprot at 2 hours to 99.39+14.43UN/mgprot and 117.45 + 15.32UN/mgprot at 6 hours, respectively; reduced plasma NO from 29.45+3.92umol/L and 23.70 + 3.68umol/L at 2 hours to 34.90+5.46umol/L and 26.58+ 4.48umol/L at 6 hours, respectively; improved number of neuron in hippocampus region from 43.00 + 1.00 and 48.20 + 1.3 at 2 hours to 26.8 + 2.59 and 34 + 1.22 at 24 hours, respectively; improved NSS 5.67+1.03 and 4.17+ 1.17 at 24 hours. Brain tissue water content was not significantly different between treated and untreated groups. There were relation between brain edema and nitric oxide, free radical.Conclusion: We conclusion the 180mg/kg IP ketamine was effective in ameliorating neurological dysfunction after head cold injury, maintaining brain tissue SOD activity, reducing MDA, reducing NOS level, reducing plasma NO and improving neuron survive; but ketamine did not reduced brain edema.