The Role And Alteration Of Oligodendrocyte Lineage Cells In The Early Phase Radiation-induced Brain Injury In Rats

At present, radiotherapy remains a major, sometimes the only treatment modality for primary and metastatic brain tumors as well as head and neck cancers which account for 1/3 of all tumors in patients. In addition to antineoplastic therapy, there is the increasing application of radiation in the management of arteriovenous malformations (AVMs) and other non-tumor disorders of the central nervous system (CNS), such as epilepsy. But the radiation-induced brain and spinal cord injury that occurs in the early and late phase after irradiation will make the life quality of patients decline and limit the extensive application of radiotherapy to CNS tumors. To explore the precise mechanism and protective drugs of radiation-induced brain injury will contribute to the progression of Radiological Medicine and Neoplastic Radiological Therapeutics with much theoretical and applied importance.Oligodendroglial lineage cells and endothelial cell have been implicated as radiation target cells in several researches. Subacute radiation response of CNS relates to the transient demyelination in the early phase after ionizing irradiation. Late radiation response involves white matter pathology, delayed demyelination and the loss of oligodendrocyte lineage cells. From the above, it suggests that the radiation response of oligodendrocyte lineage cells is one of the major responses of CNS tissues and maybe the important factor associated with the radiation-induced brain injury and repair. So, to study the radiation response, especially the early phase alteration, will help elucidate the mechanism of radiation-induced injury and respair and provide theoretical basis for early preventation.1 The early phase radiation response of oligodendrocyte lineage cells.Objective: To examine the distribution characteristic of oligodendrocyte lineage cells (including oligodendrocyte progenitors, immature oligodendrocytes and mature oligodendrocytes) in normal adult rat brain tissues. To investigate the early phase radiation response of oligodendrocyte lineage cells in vivo in adult rats and to analyze its relationship with the radiation-induced brain injury and repair. Methods: The rat model of whole-brain radiation is established with the brain of healthy adult rats exposed to 4 MeV x-ray with single-dose 30 Gy, 10 Gy, 2 Gy and 0 Gy respectively. To examine the expression of NG2, O4, CNPase and MyTl in the cortex of rats brain by immunohistochemistry and take count of the positive cells at the time-points of 1, 3, 7, 14 and 28 days after ionizing irradiation, and to analyze the correlationship wiA radiation doses. Results: 1. The rats in 30 Gy group denuded in the radiation fieW obviously around 20 days after irradiation. There was no statistical difference in body weights and neurological behavior evaluation between each group. 2. There were a lot of NG2 or O4-positive cells in the cerebral cortex of rats in 0 Gy group. At 1 day post-radiation, the number of NG2 and O4-positive cells of rats in 2 Gy group had no obvious change comparing with that of 0 Gy group, however, the number of NG2 and O4-positive cells of 10 Gy and 30 Gy groups decreased significantly. The NG2 and O4-positive cells at the time-points of 7 and 14 post-radiation increased most and the positive cells in 2 and 10 Gy groups were more than that in 0 Gy group. At 28 day after irradiation, the number of NG2 and O4 positive cells reduced in different degree in each group. The increase rate of NG2 and O4 positive cells at each observing time-point correlated negatively to the radiation doses. 3. There were many CNPase positive cells evenly distributed in the cerebral cortex of rats in 0 Gy group. The CNPase positive cells in the cerebral cortex of rats in 10 and 30 Gy groups diminished significantly at 1 and 3 day after irradiation comparing with that of 0 Gy group, and no significant difference between each group at other time-points. The increase rate of CNPase positive cells at each observing time-point also correlated negatively to the radiation doses. 4. There were a few MyTl p...