Effects of single low dose irradiation on subventricular zone cells in juvenile rat brain

Abstract

Although the juvenile human brain is relatively radioresistant, irradiation can result in brain growth retardation, progressive mental disturbance, and neurologic abnormalities. As neural stem cells or progenitor cells may be a target of radiation injury and may play an important role in the brain's functional recovery, we examined the effects of whole brain irradiation on these cells in juvenile rat. Six-week-old Wistar rats, where the brain is still growing, were irradiated with single doses of 1, 2, or 3 Gy X-ray. We measured their body and brain weights at 30 or 60 days after irradiation. The chronological changes of the subventricular zone (SVZ) were examined at 6 h, 2, 7, 14, 30, or 60 days after irradiation by immunohistochemistry, specifically looking at the neural stem cells or progenitor cells using anti-nestin antibodies specific for these cells. The rate of brain weight gain of irradiated rats significantly decreased in comparison to controls, although that of body weight gain was similar among them. Multiple apoptotic cells appeared in the SVZ at 6 h after irradiation with simultaneous reduction in nestin-positive cells (69% of the control). The cell levels recovered within a week, with the nestin-positive cells reaching maximal numbers (182%) on Day 14. Nestin-positive cells returned to baseline levels within 30 days (96%) and remained unchanged for the subsequent 60 days. The X-ray dosage did not affect these findings. Our findings revealed that single low dose X-ray administration reversibly affected the levels of neural stem and progenitor cells in the SVZ region. These results suggest that continuous multiple administrations of X-rays in clinical treatment may affect irreversible changes on neural stem or progenitor cells, causing brain growth retardation, or dysfunction.