Irradiation of the brain does not only bear the risk of inducing acute (partially mass-associated) side effects such as nausea, vomiting and fatigue, but also causes long-term neurocognitive deficits. Although neurocognitive disorders after PCI/Whole brain radiotherapy (WBRT) also have a multifactorial etiology based on a patient's individual medical history (preceding chemotherapy, pre-existing vascular damage e.g. from smoking, local reactions/edema), it is currently believed that they are mostly caused by a loss of neural stem cells in the hippocampal areas. Multipotent and self-renewing neural stem cells are found in the subgranular zone of the adult hippocampus and in the subventricular zone of the lateral ventricles. The hippocampus plays an important role in memory consolidation and emotional learning (contextual fear conditioning). The disruption of neurogenesis in the subgranular zone or damage to the hippocampus can lead to impaired short- and long-term memory, learning and contextual fear conditioning. In line with this, irradiating the brain decreases neurogenesis in the hippocampus which leads to impaired hippocampal-dependent learning and memory.