Decreased neurogenesis after brain exposure to ionizing radiation is linked to neurocognitive impairments. Using transgenic mouse models, we previously showed that abrogation of radiation-induced senescence, or apoptosis, can partially rescue neurogenesis in the subventricular and hippocampus regions. Here, we evaluate whether the injection of recombinant epidermal growth factor (rEGF) or mesenchymal stromal cells (MSC) engineered to secrete EGF (MSC-EGF) can preserve neurogenesis. Using doublecortin (Dcx) expression and BrdU incorporation assays, we found that the injection of rEGF into the subventricular zone (SVZ) promotes neurogenesis, despite increasing apoptosis, in the brain of irradiated mice. The effect of rEGF was mostly localized, as Dcx expression was not induced in the hippocampus region and limited in the contralateral SVZ. Surprisingly, the injection of bone marrow-derived MSC alone, or secreting EGF, did not result in increased neurogenesis despite the fact that part of the MSC survived a few weeks after injection. Our results suggest that only a supraphysiological concentration of rEGF can promote neurogenesis, likely through a direct mitogenic effect.

大脑暴露于电离辐射后神经发生减少与神经认知障碍有关。我们以前使用转基因小鼠模型表明，消除辐射诱导的衰老或细胞凋亡可以部分挽救脑室下和海马区的神经发生。在这里，我们评估了注射重组表皮生长因子 (rEGF) 或设计为分泌 EGF (MSC-EGF) 的间充质基质细胞 (MSC) 是否可以保护神经发生。使用双皮质素 (Dcx) 表达和 BrdU 掺入测定，我们发现将 rEGF 注射到脑室下区 (SVZ) 中，尽管增加了细胞凋亡，但在辐射小鼠的大脑中促进了神经发生。rEGF 的作用主要是局部的，因为 Dcx​​ 表达不在海马区诱导，而在对侧 SVZ 中受到限制。令人惊讶的是，尽管部分 MSC 在注射后存活了几周，但单独注射骨髓来源的 MSC 或分泌 EGF 并没有导致神经发生增加。我们的结果表明，只有超生理浓度的 rEGF 才能促进神经发生，这可能是通过直接的有丝分裂作用实现的。