Preliminary Study On Magnetic Resonance Imaging Of Fe₃O₄@Gd₂O₃:Tb³⁺@SiO_x Nanoparticles After Cerebral Ischemia-reperfusion Injury In Rats

Objective:Preliminary investigation of the magnetic resonance imaging characteristics of Fe₃O₄@Gd₂O₃:Tb³⁺@Si O_xnanoparticles after cerebral ischemia-reperfusion injury in rats.This study was conducted to investigate the optimal imaging characteristics of magnetic resonance imaging after cerebral ischemia-reperfusion injury with nanoparticles of different concentrations at different times,in order to explore the optimal imaging with nanoparticles of appropriate concentration at appropriate time.Methods:In the first stage,20 SD male rats（250-300g）were divided into 4 groups of 5 rats each at different concentrations of 4mg/kg,8mg/kg,12mg/kg and 15mg/kg,and the brain ischemia-reperfusion injury model was established by the wire bolus method,and magnetic resonance scans were performed 72h after the injection of different concentrations of nanoparticles,respectively.In the second stage,20 SD male rats（250-300g）were divided into 4 groups,sham-operated group,MCAO/R+saline group,MCAO/R+15mg/kg24h group,MCAO/R+15mg/kg48h group,5 rats in each group,and the model was established by the wire bolus method,and MRI scans were performed at different times after the injection of 15mg/kg nanoparticles.After magnetic resonance scanning,the rats in the MCAO/R+saline and MCAO/R+15mg/kg72h groups were executed and subjected to WB detection and Prussian blue staining.The imaging characteristics of cerebral ischemia reperfusion injury model in rats were statistically analyzed by different times and concentrations of nanoparticles;whether the nanoparticles had toxic side effects and aggravated the injury situation in rats were studied by the analysis of WB detection;the phagocytosis of cells with phagocytosis function in brain was summarized by analyzing the characteristics of Prussian blue staining images.Results:1.Zea-longa score results:no neurological deficits were found in the sham-operated group,while neurological deficits were found in all the remaining groups.Except for the sham-operated group,there was no significant difference in the neurological function scores among the groups after modeling（P>0.05）.2.Magnetic resonance imaging:with the increase of concentration,the relative abnormal signal intensity on T₁image gradually increased,and the relative abnormal signal intensity on T₂image gradually decreased,and the contrast effect became more and more significant（P<0.05）,and the contrast effect was best at 15 mg/kg;With the extension of time,the relative abnormal signal intensity on the T₁image of magnetic resonance gradually increased,and the relative abnormal signal intensity on the T₂image gradually decreased,and the visualization effect became more and more significant（P<0.05）,and the best developing effect was achieved at 72 h.3.WB test:between the two groups of rats,although the expression level of TNF-αdecreased in the nanoparticle group,the WB assay results suggested that there was no significant difference in TNF-αexpression（P>0.05）.4.Prussian blue staining:Prussian blue iron staining showed that the iron particles in the cells were dyed blue,indicating that the nanoparticles were engulfed by the phagocytes in the brain,but the number of phagocytic cells is small.Conclusion:Fe₃O₄@Gd₂O₃:Tb³⁺@Si O_xnanoparticles could be used for the development of cerebral ischemia-reperfusion injury model,and the best development was achieved at an injected concentration of 15 mg/kg;compared to other groups,the best development was achieved at 72 h.WB assay showed that the nanoparticles did not aggravate the inflammatory response and did not cause increased injury in rats.Prussian blue staining showed the phenomenon of phagocytosis of nanoparticles in the brain.