Alterations in the rat forebrain apoptosis following exposure to ionizing radiation

Abstract

Ionizing radiation commonly used in the radiotherapy of brain tumours can cause adverse side effects to surrounding normal brain tissue. The most significant response of adult brain to radiation damage is induction of apoptosis. The adult mammalian subventricular zone (SVZ) of the brain lateral ventricles (LV) and their subsequent lateral ventricular extension, the rostral migratory stream (RMS), is one of the few areas, which retains the ability to generate new neurons and glial cells throughout life. Taking into account the fact, that ionizing radiation is one of the strongest exogenous factors affecting cell proliferation, the aim of the present study was to investigate the occurrence of radiation-induced apoptosis in this neurogenic region. Adult male Wistar rats were investigated 1, 5 or 10 days after single whole-body gamma irradiation with the dose of 3 Gy. Apoptotic cell death was determined by in situ labelling of DNA nick ends (TUNEL) and fluorescence microscopy evaluation of TUNEL-positive cells. Considerable increase of apoptotic TUNEL-positive cells was observed 24 hrs after irradiation in caudal parts of RMS; i.e. in the vertical arm and elbow of RMS. Initial increase was followed by strong reduction of apoptosis in the RMS and by secondary over-accumulation of apoptotic cells in the animals that survived ten days after exposure. Results showed, that the proliferating population of cells, arisen in SVZ are highly sensitive to radiation-induced apoptosis. This observation should have implications for clinical radiotherapy to avoid complications in therapeutic brain irradiation.

Long-term alterations of cell population in the adult rat forebrain following the exposure to fractionated doses of ionizing radiation

“…More expressive changes were seen in the vertical arm and the elbow, and few or virtually no proliferating cells were found in the horizontal arm. In another set of experiments we performed detection of fragmented DNA using terminaldeoxynukleotidyl tranferase-mediated dUTP-biotin nick end labeling (TUNEL) method and we found radiation-induced increased rate of apoptosis in course of ten days after irradiation (Bálentová et al 2011). Taking into account these previous data, our simultaneous assessment of proliferating and apoptotic cells showed that proliferation activity surpassed a rate of apoptosis except of the most distant region along the SVZ-OB axis.…”