This suggests that it is not the number of neural stem cells that is critical ; rather, their functionality plays a crucial role in decreasing hippocampal neurogenesis after BI, which is caused by incompletely repaired DNA damage, microvascular angiogenesis disruption, neuroinflammation, and oxidative stress. Because pretreatment with EA attenuated oxidative stress in the ischemia-reperfusion model and continuous treatment with EA increased BDNF and glial cell-line-derived neurotrophic factor expression, future studies should apply an optimized EA protocol after lower dose irradiation to test its ability to restore hippocampal neurogenesis. Similar to EA, CCR2 deficiency, L-158,809, and ramipril Torin 1 inquirer prevent cognitive impairments, but do not influence neurogenesis. Usually, the role of hippocampal neurogenesis in learning and memory is explored by decreasing neurogenesis with irradiation, antimitotic drugs, and mutational approaches, whereas neurogenesis is increased by environmental enrichment and voluntary running. It should be noted that these ASP1517 HIF inhibitor approaches do not only affect neurogenesis; for example, irradiation also affects neuronal architecture. Thus, negative reports regarding hippocampal neurogenesis should be considered. For example, the toxin methyl azoxymethane acetate decreases neurogenesis; however, this antimitotic agent only impairs one kind of hippocampal-dependent memory, while two forms of hippocampal-dependent learning and memory are not affected. Interestingly, X-ray irradiation and genetic overexpression of follistatin, both of which severely impair hippocampal neurogenesis, prolong the hippocampus-dependent periods of remote contextual fear memory, whereas running-wheel exercises that promote hippocampal neurogenesis speed up the decay rate of this kind of memory. Therefore, the exact role of hippocampal neurogenesis in cognition warrants further research. Long-lasting reductions in dendritic complexity and spine density, together with alterations in spine morphology and synaptic protein composition, are observed even after a very low irradiation dose. In the present study, synaptophysin expression was used to assess postirradiation neuronal connectivity impairments. Synaptophysin, a 38-kDa glycoprotein localized in synaptic vesicle membranes, is important for docking, fusion, and endocytosis and is a useful presynaptic marker. EA restored synaptophysin expression, indicating that EA prevented synaptic loss after irradiation. Given the important role of structural plasticity in learning and memory, it is possible that synaptic loss, instead of hippocampal neurogenesis, contributes to BI-induced cognitive impairments. However, further studies are needed to test this hypothesis. EA is an economic and easy-to-administer technique with few adverse effects and has been efficacious for some cancer therapy-related side effects including fatigue and chronic xerostomia. Our results demonstrate that EA can also prevent irradiation-induced cognitive impairments. A clinical trial should be designed to test the efficacy of this ancient treatment in patients undergoing BI. It should be noted that EA protected the BBB after BI, which may influence chemotherapy delivery to the CNS. However, the BBB studied here was in normal brain tissue as opposed to brain tumor tissue. Thus, whether EA will affect local tumor control must be assessed in future studies.