Abstract: BACKGROUND: Glioblastoma is a common malignant brain tumor for adults with poor prognosis and remains lack of efficient treatments. 
OBJECTIVE: To investigate the efficacy of single high-dose radiotherapy on glioblastoma and the feasibility of oligodendrocyte progenitor cells in the repair of radiation-induced brain injury.
METHODS: Plasmid transfection was used to develop human U-87 MG cell line expressing luciferase (Luc). Fifteen Fisher 344 rats bearing Luc-U-87 MG glioblastoma were randomly divided into tumor model group (n=3), radiotherapy group (n=6), and oligodendrocyte progenitor cell transplantation group (n=6). Single high-dose radiotherapy (80 Gy) was given in the latter two groups and cell transplantation was performed in the last group 5 weeks after radiotherapy. In vivo imaging was employed to monitor the tumor growth. MRI was performed to observe the cerebral structure changes induced by radiation. Kaplan-Meier analysis was used to determine the effect of cell transplantation on the survival rate of irradiated rats. Survival and differentiation of transplanted cells were histologically observed. 
RESULTS AND CONCLUSION: In vitro imaging results showed that the transfected U-87 MG cells reacted with the Luc substrate to produce bioluminescence signals. Signal intensity had a positive linear correlation with the number of transfected cells. Intracranial glioblastoma signals in the tumor model rats continued to increase until their death at 5 weeks after tumor inoculation. Two weeks after radiotherapy, the bioluminescence signal started to decline in the radiotherapy group and was not detected at 4 weeks. Necrotic tumor tissue was observed on T2WI at 5 weeks after radiotherapy but not at 10 weeks, at which timepoint the abnormal signal indicative of brain injury appeared. However, there were no similar signals in the cell transplantation group. Fifteen weeks later, T2WI showed hypo- and hyperintensity signals in the brain parenchyma for all the rats which received irradiation, whereas the injury signal in the radiotherapy group was stronger than that in the cell transplantation group. The survival analysis results revealed the median survival time of the tumor model group, radiotherapy group, and cell transplantation group were 30, 114.5, and 232.5 days, respectively. There were significant differences in the median survival time among groups (P < 0.01). Histological findings showed the transplanted cells survived with multipolarity and some of them expressed myelin basic protein. Moreover, the expression of myelin basic protein in the cell transplantation group was significantly higher than that in the radiotherapy group (P < 0.01). All these findings indicate that single high-dose radiotherapy can effective treat human-derived glioblastoma in rats. Oligodendrocyte progenitor cells transplanted are capable of repairing radiation-induced brain injury, thereby prolonging the survival of irradiated rats. Remyelination is one of the mechanisms accounting for brain tissue repair.  

Key words: glioblastoma, radiotherapy, radiation-induced injury, oligodendrocyte progenitor cell, remyelination, survival time, MRI, rat