| Objective:Because of its high morbidity and high mortality rate and disability rate, stroke is paidmore and more attention. The common causes of ischemic stroke is the middle cerebralartery occlusion (MCAO). Ischemic injury followed by a series of pathological cascade inwhich inflammation was one of the more important reaction process. Brain ischemictolerance (BIT) was to give the body small doses of harmful stimuli, that is cerebralischemic preconditioning (CIP), which could obviously reduce brain cell damage causedby the subsequent severe cerebral ischemia. Endogenous neuroprotective effect of thisphenomenon demonstrated for the neuroprotective mechanism of cerebral ischemia whichprovided a new idea. Exisiting research has been confirmed that inflammatory mediatorsplay an important role in brain ischemic tolerance. Tumor necrosis factor-like weakinducers of apoptosis(TWEAK) is an inflammatory factor which can induce the expressionof multiple gene products in the inflammatory reaction. After cerebral ischemia,TWEAKregulate the expression of matrix metalloproteinase9(MMP-9) by activating nuclearfactor-κB (NF-κB) signaling pathway, thus affecting the neurovascular unit (NVU).Ischemic preconditioning inhibit the NF-κB pathway through regulation of inflammatoryfactors and cytokines increase or decrease, which results in the brain ischemic tolerancehaving a protective effect on the nervous system. In this study, the cerebral ischemia modelcaused by the middle cerebral artery occlusion, TWEAK, NF-κB and MMP-9expressionwas observed after ischemic preconditioning in rat brain ischemia model to investigate theneuroprotective effect of ischemic preconditioning and the relations of TWEAK,NF-κB,MMP-9and ischemic tolerance. Methods:The healthy adult male SPF Sprague-Dawley rats were randomly divided into theexperimental group, the control group, the sham group and the normal group.The middlecerebral artery was blocked by line to produce the rat focal cerebral ischemia model,MCAO10min as IP. Permanent middle cerebral artery occlusion (PMCAO) model wasmade after IP48.After the neurological score, the rats were sacrificed at different timepoints respectively at6h,24h,48h,72h after PMCAO. Brain water content wasmeasured by Wet and dry weight method and the volume of cerebral infarction wascalculated using2%2,3,5-triphenyltetrazolium chloride triazole (TTC) staining method.TWEAK, NF-κB and MMP-9expression was detected by immunohistochemistry andreverse transcription polymerase chain reaction (RT-PCR).Results:1.Left limbs hemiplegia symptoms of varying degree showed in the experimentalgroup and control group rats awake after anesthetization. Neurological deficit symptoms inthe experimental group significantly reduced than the control group (P <0.05),withoutsimilar symptoms in sham group.2. There was significant difference of brain water content between the experimentalgroup and control group (P <0.05); A significant difference existed between theexperimental group and the sham group,similarly in the control group and sham group (P<0.01).3. TTC staining showed uniform and red dye in the sham group and normal groupbrain tissue without infartion,on the contrary, white brain infarcts was observed in theexperimental group and control group.The infarction volume in the experimental groupwas significantly less than the control group,and the comparison between the experimentalgroup and control group had statistical difference (P <005).4.The TWEAK, NF-κB and MMP-9protein expression: the number of positive cellsincreased at6h after cerebral ischemia,with a significant difference compared with thesham group.The number of positive cells reached a peak at24h.The number of positivecells at48h decreased comparing with24h, then72h droped lower. Compared with thecontrol group, the number of positive cells in the experimental group was significantlyreduced. The protein expression of TWEAK、NF-κB and MMP-9at each time point afterinfarction showed a significant positive correlation.5. The TWEAK, NF-κB and MMP-9mRNA expression: The mRNA expression at6hafter brain ischemia in the experimental group had a significant difference compared withthe sham group.The mRNA expression reached a peak at24h, declined at48h and dropped lower at72h,but there was still differences compared with the sham group at72h. Theexpression of mRNA in experimental group is less than the control group and thedifference was statistically significant. The mRNA expression of TWEAK, NF-κB andMMP-9at each time point after the infarction showed a significant positive correlation.Conclusion:The expression of TWEAK, NF-κB and MMP-9was significantly elevated in braintissue after cerebral ischemia and there was a close correlation between each other.Ischemic preconditioning could improve the neurological symptoms, lessen cerebral edema,reduce the infarct volume and inhibit the TWEAK, NF-κB and MMP-9expression aftercerebral ischemia.Ischemic preconditioning produce ischemia tolerance havingneuroprotective effects against focal cerebral ischemia. TWEAK, NF-κB or MMP-9maybe associated with this neuroprotective mechanism. |
PDF Full Text Request