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

Abstract

We investigated radiation-induced delayed alterations of proliferating population, cells undergoing apoptosis and glial cells housed rat brain neurogenic region. Adult male Wistar rats were investigated 30, 60 or 90 days after whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Using immunohistochemistry for detection of cell proliferation marker Ki-67, caspase3 as apoptotic marker and GFAP for mature astrocytes we have been performed quantitative analysis in different forebrain's areas along the SVZ-OB axis, i.e. in the anterior subvetricular zone (SVZa), vertical arm, elbow and horizontal arm. In animals that survived thirty days after radiation treatment initial decrease of the Ki-67-positive cells was seen in regions along the SVZ-OB axis. The highest increase was observed in vertical arm on the 60th day followed by the most striking decline on the 90th day after irradiation. Cells undergoing apoptosis didn't showed expressive increase during entire experiment except of horizontal arm. The most striking changes of GFAP-positive cells were seen 30 and 60 days after irradiation in vertical arm and elbow. Results suggested that radiation response of proliferating cells and astrocytes resides the SVZa may play contributory role in development of more adverse radiation-induced late effects.

Effect of Fractionated Irradiation on the Hippocampus in an Experimental Model

“…Since a small fraction of all FJ-B neurons were double-labelled by TUNEL, it is not clear whether a large proportion of re- In both investigated areas, there was a relatively low decrease in the numbers of GFAP-IR cells, more evident at 30 days after treatment. This is in discrepancy with our previously published studies that revealed strong short and long lasting astrocytic response after fractionated irradiation with low overall doses (3, 4 Gy) [14,28]. Brain lesions generally increase SVZ neurogenesis or gliogenesis and cause SVZ cell emigration to ectopic locations [29].…”

“…In our experiment, the steep increase in rate of neurodegeneration was more evident in the group investigated 30 days after irradiation. This fact is particularly comparable with our previous fi nding about increased apoptosis in the neurogenic subvetricular zoneolfactory bulb axis (SVZ-OB axis) of rats investigated up to three months after fractionated irradiation [14]. Experiments done before showed, that single irradiation with various radiation doses (2-10 Gy) dramatically increased the numbers of apoptotic cells in the hippocampal DG 3-6 hours after exposure.…”

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

“…Despite different dose fractions and survival times, our experimental studies in rats revealed a clear astrocytic response [ 51 , 77 , 78 ]. Fractionated irradiation with a total dose of 3 Gy (1 Gy/d, 1 d/week for 3 weeks) resulted in a significant enhancement of the GFAP-labelled astrocytes in the RMS two weeks after treatment.…”

“…Following irradiation with a total dose of 4 Gy (1 Gy/d, 1 d/week for 4 weeks), a significant increase of astrocytes was dominated 60 days after treatment, but in the end of the experiment the numbers returned back to control values ( Figure 3 ). (Reproduced from [ 78 ] with the permission of the journal General Physiology and Biophysics).…”