| Backgroud and purposeCerebral infarction is a more common form of cerebrovascular disease,including two types of ischemic cerebral infarction and hemorrhagic cerebral infarction.The former is more common,accounting for about 85%of patients with cerebral infarction,and the mortality rate is high.Patients will have sequelae of varying degrees in the later stages,which seriously affects the patient's quality of life and family happiness.With the improvement of the level of clinical treatment,the clinical treatment of cerebral infarction has become more comprehensive.In recent years,the intervention and treatment of secondary nerve damage and functional and metabolic abnormalities in the distant area after cerebral infarction have attracted wider attention.The proposal of the diaschisis theory explains many clinical symptoms of abnormal tissue structure,functional metabolism,and electrophysiological activity that occur in the distant region after cerebral infarction.More and more researchers rely on more advanced electrophysiology,pathology and imaging technology.Further research on the causes and development mechanisms of neurological inability to connect,and to focus more attention on the occurrence of infarction,and to artificially interfere with the inability of neural connections to generate pathways or mediators to alleviate the infarct's primary lesions on the surrounding and The influence of the structure and function of the distant region provides a more efficient treatment approach and new methods for the recovery of neural function networks.Repulsive guidance molecule b(RGMb)is an important axonal growth inhibitor that plays a role in inhibiting axon regeneration and remodeling in the central nervous system.In vitro experiments have shown that the expression of RGMb increases after cerebral infarction.It directly participates in the process of neuron degeneration and apoptosis in the infarcted area and the distant region with which the neuron is connected.Related studies have shown that RGMb participates in mediating the generation of the inability of diaschisis.Therefore,RGMb is a kind of The neuron regeneration inhibitory protein with great potential has a great clinical value in the regulation of neural function network after cerebral infarction or other central nerve injury through clinical targeted intervention.Diffusion kurtosis imaging(DKI)is a non-invasive magnetic resonance imaging technology based on the measurement of water molecule motion.It is based on diffusion weighted imaging(DWI)and diffusion tensor imaging(DTI),and can be extended to study advanced technology of non-Gaussian water diffusion model.Compared with DTI,its increased kurtosis value is more sensitive to the observation of fine structures of complex structures.In this study,DKI technology was used to detect the infarcted core area and bilateral cerebellar imaging parameters in rats with ischemic cerebral infarction,to prove the existence of neurological inability after cerebral infarction,and to explore the phenomenon by combining pathology and immunohistochemistry The causes and improvement methods provide a more reliable basis for the improvement of clinical treatment methods.Materials and Methods1.Randomly divide 144 SD rats into group A(sham operation group without inserting thread plug)and group B(MCAO group,i.e.model group),group C(negative control group,directed implantation of empty adenovirus after MCAO model creation),group D(intervention group,directed implantation of recombinant adenovirus Adv-RGMb-siR after MCAO model production):There were 12 in group A,60 in group B(12 in each time point at 6h,12h,24h,48h and 3d),36 in group C(12 in each subgroup at 3 time points at 12h,24h and 48h)and 36 in group D(12 in each subgroup at 3 time points at 12h,24h and 48h).2.Neural function scores and magnetic resonance scans(sequences including T1WI,T2WI,DWI,and DKI)were performed on rats in groups A,B,C,and D,and post-processing of DKI images was performed to obtain the infarct core area(left basal ganglia area)MK and MD images of bilateral cerebellar hemispheres,and process and record parameters;3.Six brain samples were randomly selected from each group of rats at each time point for HE staining and immunohistochemistry,and the expression of RGMb protein in the infarcted core region(left basal ganglia region)and bilateral cerebellar hemispheres was measured;4.SPSS 21.0 statistical software was used.Pairwise comparison was performed using independent sample t-test or Mann-Whitney U;comparison of multiple groups of samples can be performed by one-way analysis of variance or Kruskal-Wallis rank sum test.Multiple comparisons between groups were performed using the LSD-t test or the Bonferroni test.Think P<0.05 is statistically significant.Results1.In the MCAO group,the MK values of the core infarcted area and bilateral cerebellar hemispheres at 6h,12h,24h,48h,and 3d were higher than those of the control group and were highest at 12h;MD values were lower than those of the control group and were lowest at 12h(P<0.05);2.In the MCAO group,the MK values of the contralateral cerebellar hemispheres were higher than that of the ipsilateral cerebellar hemispheres at 6h,12h,24h,48h,and 3d(P<0.05);3.In the RNAi intervention group,the MK values of the core infarcted area at 12h,24h,and 48h were lower than those of the MCAO group,and the MD value of the core infarcted area at the 24h and 48h of the intervention group was higher than that of the MCAO group(P<0.05);compared with the MCAO group,the MCAO group was compared with the negative control group.There is no statistically significant difference in MK value and MD value;4.The MK value of the contralateral cerebellar hemisphere at 24h and 48h in the RNAi intervention group was lower than that of the MCAO group,and lower than the MK value of the ipsilateral cerebellar hemisphere(P<0.05);5.The expressions of RGMb in the core infarcted area(6h,12h,24h,48h,3d)and bilateral cerebellar hemispheres(12h,24h,48h,3d)of MCAO group were higher than those of the control group(P<0.05);In contrast,the expression of RGMb on the contralateral cerebellar hemisphere(12h,24h,48h,3d)was higher than that on the ipsilateral cerebellar hemisphere(P<0.05);6.The RGMb expression in the core infarction area and the contralateral cerebellar hemisphere(12h,24h,48h)and ipsilateral cerebellar hemisphere(24h,48h)was lower in the RNAi intervention group than in the MCAO group.Cerebellar hemisphere(P<0.05);7.MK value and MD value change rate before and after RNAi intervention:In comparisons with statistically significant differences,the MK value change rate is higher than the MD value.Conclusions1.DKI can be used to detect the crossed cerebellar diaschisis,and MK value is more sensitive than MD to detect diaschisis after cerebral infarction.;2.The change in the expression level of the repulsive guidance molecule b can prompt the existence of the crossed cerebellar diaschisis;3.After the RGMb-specific RNAi intervention,the RGMb expression in the infarcted core and contralateral cerebellum decreased,the MK value decreased,and the MD value increased,indicating that this treatment method has positive therapeutic significance for the diaschisis after cerebral infarction. |
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