Repairing the neuronal cell damage induced by ionising radiation via immune response

Although radiotherapy (RT) is used in the treatment of many cancer types, it also exerts its devastating effect on healthy tissues other than the cancer cells or tissues. The hippocampus (HP), which is closely related to various cognitive functions such as learning and memory, is adversely affected by irradiation. How stem cells and differentiated cells in HP respond to damage caused by radiation exposure and by which factors these responses work is still largely unknown. The aim of the current study was to examine the effect of RT from different angles in-vitro using HT22 cells obtained from mouse HP, and then to repair the aversive effects of irradiation by using an immune response approach (with paracrine effects found in the macrophage cell line RAW264. In this study, it was shown that 2 Gy and 8 Gy doses of ionizing radiation to HT22 cells caused cellular loss, permanent morphological alterations and an increase in the expression of genes that are effective in the anti-inflammatory response, such as Nrf2 and Grn. Based on the findings of survived colony numbers, real-time cell analysis and apoptosis, the most efficient treatment groups among the others were designated as the group that was treated with the conditioned media of macrophages both 24 hr before and after the irradiation. After selecting this group, the biological responses of the treatment group, which included the immunotherapy approach to radiation at 48th and 72nd hours were evaluated. It was determined that the treatment group caused a decrease in the number of viable cell colonies and apoptosis rate in response to 8 Gy radiation damage. In this thesis, the effects of radiation on HT22 cells were evaluated in detail, and promising preliminary results were obtained that immunotherapy approaches could be protective against radiation damage. In future studies, this effect on neural cells can be tested in vivo and the potential protective and/or restorative effect of the conditioned medium can also be tested on biological systems.