| ObjectiveEpilepsy is a common neurological disorder characterized by spontaneous recurrent seizures(SRSs),which affects patients' health severely.Currently the main therapies for epilepsy are surgery and drugs,whereas approximately 30%of patients are resistant to antiepileptic drugs.TLE is the most common type of drug-resistant epilepsy.It is an urgent need to explore new treatments of TLE for clinical applications.With continuous improvement of stem cell technology,stem cells demonstrated promising therapeutical potential in regenerative medicine area.Neural stem cells(NSCs)are a class of cells that can differentiate into various types of cells in the central nervous system,which have been gradually used in preclinical experimental studies of neurological diseases.Induced pluripotent stem cells(iPSCs)can differentiate into other types of cells,which can avoid ethical issues,immune rejection etc.,thus,made it an ideal approach for neurological diseases.This study aimed to use spatiotemporal 18F-FDG PET imaging studies to investigate the dynamic metabolic changes after NSCs and iPSCs transplantation in a rat model of TLE.MethodsTLE was established by intrahippocampal kainic acid(KA)administration.Twenty-eight male rats were randomly assigned to one of the 4 groups:iPSCs,NSCs,KA-phosphate-buffered saline injection(E-CTR),and sham-surgery control(CTR).Serial 18F-FDG micro-PET imaging was performed weekly to investigate the dynamic metabolic changes,video-electroencephalography(Video-EEG)were recorded daily to monitor the frequencies and seizure durations in rats.Hematoxylin-eosin staining,immunohistochemical and immunofluorescent analyses were performed after the last PET study.Selected markers were as follows:neuronal nuclei(NeuN),glial fibrillary acidic protein(GFAP),gamma amino butyric acid(GABA),neuropeptideY(NPY),Glucose Transporterl(GLUT-1).ResultsThe frequency of SRSs in the NSCs and iPSCs group were significantly lower than that of E-CTR group(P<0.05)from Week 3 to Week 6.The frequency of SRSs in the NSCs group was lower than that of iPSCs group(P<0.05)at Week 5.The seizure duration in both stem cell-treated groups were significantly shorter than that of E-CTR group at Week 6(P<0.05).18F-FDG micro-PET studies demonstrated significantly higher 18F-FDG accumulation in the hippocampus in the NSCs and iPSCs group compared with the E-CTR group(P<0.05)at Week 3.At Week 5,glucose metabolism changes in the NSCs group were significantly higher than those in the other three groups(P<0.05).18F-FDG accumulation of the NSCs group increased obviously during the 6-week period and was significantly higher than that of iPSCs group at Week 6(P<0.05).Hematoxylin-eosin staining results found the number of cells in the NSCs group was significantly higher than that of the E-CTR group(P<0.05)in biolateral area 1 of cornus ammonis(CAlarea).The number of cells in the iPSCs group was significantly higher than that of the E-CTR group(P<0.05)in the right CA1 area.The number of cells in the NSCs group and iPSCs group was significantly higher than that of the E-CTR group(P<0.05)in the left CA3 area.Immunohistochemical and immunofluorescence studies found that transplanted iPSCs and NSCs survived and migrated to the injured region and expressed protein markers for cells of NeuN,GFAP,GABA,NPY,GLUT-1.In addition,there was a significant positive correlation between the PET imaging findings and the integral optical density(IOD)of GFAP(P= 0.037).However,a significant negative correlation was found between the PET imaging findings and the IOD of GLUT-1(P= 0.021).ConclusionSerial 18F-FDG PET imaging combined with Video-EEG demonstrated dynamic metabolic and functional recovery after NSCs and iPSCs translation in a rat model of TLE.Compared with iPSCs,NSCs transplantation reduced the seizure frequency and improved the recovery of cerebral glucose metabolism.NSCs transplantation seemed to be a better potential therapeutic approach than iPSCs. |
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