Effect of microglia/macrophage pre-activation on TLR2/NF-κb signaling pathway early after ischemic brain injury in rats / 中华创伤杂志

ABSTRACT

Objective To investigate the effect and significance of microglia/macrophage activation prior to cerebral ischemic preconditioning (CIP) in regulating toll-like receptors 2 (TLR2)/nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in early stage after ischemic brain injury in rats.Methods Thirty healthy male SD rats were selected and divided into normal control group,sham operation group,ischemia group,intervention group and treatment group according to random number table,with six rats per group.A rat model of focal permanent cerebral infarct was established by occlusion of middle cerebral artery (MCAO).CIP was performed by local ischemia-reperfusion.Minocycline was used to inhibit microglia/macrophage activation after CIP.Features of microglia/macrophage activation after CIP were detected by immunofluorescence; mRNA expressions of predominant factors (NF-κB inhibitor α,IκB-α;tumor necrosis factor α,TNF-α) of TLR2/NF-κB inflammatory signaling pathway in parietal cerebral cortex by in situ hybridization method; death rate by Kaplan-meier survival curves; neurological deficits by a 5-point neurological scale; brain infarct size by triphenyl tetrazolium chloride (TTC) staining.Results Microglia/macrophage started activation at one hour after cerebral ischemic injury in preconditioning group and presented a significant increase at 12 hours.Speed and range of activation were higher in preconditioning group than in ischemic group.IκB-α mRNA in preconditioning group started expression at one hour.TNF-α mRNA in preconditioning group remained a low expression in 12 hours and had a significantly lower peak value as compared with that in ischemic group (P ＜ 0.05).CIP increased rat survival rate significantly,improved nerve function and reduced infarction size when compared with the ischemia group (P ＜ 0.05).Minocycline inhibited nerve protection by CIP significantly (P ＜0.05).Conclusion CIP induces rapid activation of microglia/macrophage in early period of rat cerebral ischemic injury and provides brain protection probably via inhibition of TLR2/NF-κB activity and inflammatory overreaction to cerebral ischemia.