Abstract
Radiotherapy plays a significant role in brain cancer treatment; however, the use of this therapy is often accompanied by neurocognitive decline that is, at least partially, a consequence of radiation-induced damage to neural stem cell populations. Our findings describe features that define the response of neural stem cells (NSCs) to ionizing radiation. We investigated the effects of irradiation on neural stem cells isolated from the ventricular-subventricular zone of mouse brain and cultivated in vitro. Our findings describe the increased transcriptional activity of p53 targets and proliferative arrest after irradiation. Moreover, we show that most cells do not undergo apoptosis after irradiation but rather cease proliferation and start a differentiation program. Induction of differentiation and the demonstrated potential of irradiated cells to differentiate into neurons may represent a mechanism whereby damaged NSCs eliminate potentially hazardous cells and circumvent the debilitating consequences of cumulative DNA damage.
Highlights
Cranial irradiation is a useful tool for the treatment of primary and metastatic brain tumors in adult and pediatric patients
QRT-PCR analysis showed high expression of Mki67 and Mcm2, markers associated with cell proliferation, and Egfr, the established marker for activated Neuralstem stemcell cell (NSC) (aNSCs) and NPC subpopulations
Using ImageJ software, we further determined the percentage of Ki-67-positive cells and found that Ki-67 antigen is detectable in 78% of all cells. These results indicate that most cells in culture have features of aNSC late state characterized by high expression of proliferation markers, lower expression of astrocytic markers, and undetectable expression levels of the Dcx gene [22]
Summary
Cranial irradiation is a useful tool for the treatment of primary and metastatic brain tumors in adult and pediatric patients. Malignancies in children is the second most common after leukemia [1] and intracranial or brain metastases occur in approximately 30% of all cancer patients [2]. Radiotherapy improves the lives of cancer patients; the use of this therapy is not without side effects. The effect of radiation-induced damage is multifactorial, it is believed that damage to neural stem cell populations is crucial for the pathogenesis of radiation-induced cognitive dysfunction [6,7]. In the adult mammalian brain, populations of neural stem cells (NSCs) represent the critical reservoir of regenerative cells. The adult brain contains two NSC pools located in the subventricular zone of the lateral ventricles (V-SVZ) [8]
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