EXPERIMENTAL STUDY OF RADIATION-INDUCED DEMENTIA -CHANGES IN GROWTH INHIBITORY FACTOR AFTER HEMICRANIAL IRRADIATION ON NEONATAL RAT BRAINS-

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 06454411
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: NIIGATA UNIVERSITY
• Principal Investigator: MORII Ken NIIGATA UNIV.BRAIN RES.INST., ASSISTANT, 脳研究所, 助手 (20230089)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Shigekazu NIIGATA UNIV.BRAIN RES.INST., ASSISTANT-PROFESSOR, 脳研究所, 助教授 (50143772)
• Project Period (FY): 1994 – 1996
• Keywords: radiation / rat / GIF / GFAP / MAG / アポトーシス

Research Abstract

To investigate radiation injury on normal brain in radiotherapy of brain tumors, the effects of X-irradiation on normal rat brain have been studied.
1.Neonatal rats, aged 7 days, received single doses (5,7.5,10,15Gy) of X-irradiation to the right hemicranium. At 1,2,3,4, and 5 weeks after irradiation, the changes of mRNA of myelin-associated glycoprotein (MAG), neuron specific enolase (NSE) and S-100 protein were analyzed with Northern blotting technique. The level of expression of MAG mRNA in the irradiated hemisphere was significantly low compared with that in the unirradiated hemisphere at 1 week after radiation. The levels of NSE mRNA and S-100 mRNA in the irradiated hemisphere were as same as that in the unirradiated hemisphere after 1-5 weeks after radiation. The results suggest that oligodendroglias are more sensitive to irradiation than neurons and astrocytes.
2.The changes of growth inhibitory factor (GIF) and glial fibrillary acidic protein (GFAP) after 15Gy hemicranial irradia tion were analyzed using Western blotting technique. The irradiated right hemispheres (IR), the non-irradiated left hemispheres (NIL) of the same 7-day-old rats, and the sham-irradiated right hemispheres (SIR) of the age-matched rats were examined for a period of 4 weeks postirradiation. The GIF relative level to sham control in IR was increased after irradiation, reached a maximum of 164% of the GIF level in SIR at 3 weeks postirradiation and remained at an increased level until at least 4 weeks, while the GFAP relative level to sham control in IR was increased after irradiation, reached a maximum of 152% of the GFAP level in SIR at 3 weeks postirradiation and then declined rapidly. These results indicate that GIF could play an important role in central nervous system repair following brain damage and may provide new insights into the mechanism of gliosis investigated mainly focusing on GFAP and of tissue reconstruction which is thought to be mainly controlled by neurotrophic factors.
3.Apoptosis was examined with in situ apoptosis detection kit (Oncor corporation) at 2,3,6 hours, 1,3 and 5 days post-15Gy hemicranial irradiation. In the irradiated hemisphere apoptotic cells were found in the subcortical white matter, hippocampal dentate gyrus and subependymal layr of the lateral ventricle at 3 and 6 hours after irradiation. The results suggest that apoptosis is closely related with disturbance of cerebral white matter at the acute stage for the irradiation insult.