Effect Of Ketamine On Neurons Apoptosis And Expression Of Caspase-3 And C-fos After Cerebral Ischemia-reperfusion In Gerbils

BACKGROUNDApoptosis, also called programmed cell death(PCD) , is an active death different from cellular necrosis. Caspases kindred is a proteolytic enzyme which can accelerate cellular death, adjust homeostasis, repair protein and split and kill off cells. Activation of caspases-3 will cause various kinds of cellular apoptosis. Intracranial injecting of caspases inhibitor can prevent neuron death of mice after they are exposed to temporary global or focal cerebral ischemia. As an Instantly Earlier Gene(IGE), c-fos is one of the nain quick-response protooncogenes of cells in central nervous system and serves as the intranucleus third messenger during information transmission of externalstimulus-transcription. The expression of c-fos has a lot to do with the information transmission in neural cells and the survival or death of neuro cells. In ischemia brain, the glutamic receptor activated by changes of ion distribution and the increase of intracellular Ca2* density is one of the major factors to cause ischemic cellular death. N- methyl -D- Aspartic Acid (NMDA) receptor is a passage to control the transmembran transport of Ca2+> Na+ and K+. Injecting inhibitors of NMDA receptors will significantly improve neural protection before and after temporary or continuous ischemia in brain middle artery obstruction models. Apoptosis is an important form of neur death after brain ischemia. In the animal model of global or focal cerebral ischemia, neur apoptosis phenomenon can be seen within ischemia field, especially in semdark band area, such as positive neur TUNEL staining, cytoplasm and nucleus condense, caspases gene, c-fos protooncogene, cell death suppress gene (Bcl~2) and trigger gene(bax, p53) are at high levels of expression in the early and late stages of ischemic brain. Blocking caspases kindred and c-fos protooncogene and activating Bcl-2 make ischemic injuries produce survivability.AIMSKetamine is a non-competitive inhibitor of NMDA and there are 玜ny reports about its role in cerebral protecting brains. The present study aims to detect the effect of ketamine on neurons apoptosis and expression of caspase-3 and c-fos after cerebral ischemia-reperfusion in gerbils. Then investigate the protective effect of ketamine on cerebral ischemia-reperfusion injury.MATERIALS AND METHODSThirty healthy gerbils (weighing 50-60g) were anesthetized with sodium pentobarbitaK (bolus: 45mg/kg) and randomly assigned to three groups. Sham-operative group (SO): bilateral common carotid arteries were separated but not ligated;ischemia-reperfusion Group(IR): bilateral common carotid arteries were separated and brain flows were blocked 10 min by noinvasion artery clamp;ketamine treatment group(K): ketamine lOmg/kg was injected into abdominal cavity 30min before brain ischemia. All gerbils in the three groups were killed 24h after they were exposed to brain ischemia. Then paraffin specimen sections were made after all the brain tissues were completely taken out. Apoptosis were detected by tefminal-deoxynucleotidyl transferase 昬diated nick end label ing(TUNEL) and caspase-3, c-fos were detected by imunohistochemisty. The positive cells werecounted under light microscope and then the labelling index (LI) were calculated. The data were analyzed by Excel. And t-test is elected.RESULTS(1) There were more TUNEL positive cells in IR and K group compared with SO group (p<0. 01) .TUNEL positive cells in K group are significantly fewer than those in IR group(p<0. 01) .(2) There were more caspase-3 positive cells in IR and K group compared with SO group (p<0. 01) . But caspase-3 positive cells in K group are significantly fewer than those in IR group (p<0. 01) .(3) The expression of c-fos in SO group is negative while there' s a considerable amount of c-fos expression in IR and K group (p<0.01 ) . But c-fos expression in K group are significantly fewer than those in IR group (p<0. 01) .CONCLUSIONS(DApoptosis is involved in pathological changes of neural cells when gerbils are subject to brain...