Ischemic stroke is a major cause of mortality and disability. Subventricular zone (SVZ) neurogenesis following an ischemic stroke may be beneficial for improving the outcomes. Environmental enrichment (EE) has been reported to increase neurogenesis following stroke. Growth arrest and DNA-damage-inducible protein 45 β (Gadd45b) is a crucial gene for activity-correlated neurogenesis in the adult hippocampus of mice. This study examined whether Gadd45b inhibition affects adult SVZ neurogenesis after an ischemic injury and explored the role of Gadd45b in EE-induced SVZ neurogenesis in adult male Sprague Dawley rats following middle cerebral artery occlusion (MCAO). Gadd45b expression was silenced by a lentivirus with RNA interference (RNAi). The 5-ethynyl-2-deoxyuridine (EdU) staining test was performed to detect cell proliferation. Gadd45b-RNAi after MCAO decreased SVZ proliferation and differentiation in the infarction boundary following ischemic injury, accompanied by the depressed expression of the brain-derived neurotrophic factor (BDNF). Treatment with EE following ischemic stroke upregulated Gadd45b and BDNF expressions and increased neurogenesis in the SVZ. Inhibition of Gadd45b markedly ameliorated the increased neurogenesis induced by EE. These data indicated that Gadd45b is related to SVZ neurogenesis following ischemic stroke, and Gadd45b mediates EE-induced neurogenesis via BDNF in the SVZ of rats following an ischemia stroke. These results implicate that Gadd45b can be a potential therapeutic target to enhance adult neurogenesis following cerebral ischemia.

缺血性中风是死亡和残疾的主要原因。缺血性中风后的脑室下区域（SVZ）神经发生可能有益于改善预后。据报道，环境浓缩（EE）可增加中风后的神经发生。生长停滞和DNA损伤诱导蛋白45β（Gadd45b）是成年小鼠海马中与活动相关的神经发生的关键基因。这项研究检查了Gadd45b抑制作用是否会影响缺血性损伤后的成年SVZ神经发生，并探讨了Gadd45b在成年雄性Sprague Dawley大鼠中脑动脉闭塞（MCAO）后EE诱导的SVZ神经发生中的作用。Gadd45b表达被带有RNA干扰（RNAi）的慢病毒沉默。进行5-乙炔基-2-脱氧尿苷（EdU）染色测试以检测细胞增殖。MCAO后的Gadd45b-RNAi降低了缺血性损伤后梗死灶中SVZ的增殖和分化，并伴有脑源性神经营养因子（BDNF）的表达降低。缺血性中风后的EE治疗上调SVZ中的Gadd45b和BDNF表达并增加神经发生。Gadd45b的抑制作用明显改善了EE诱导的神经发生增加。这些数据表明，Gadd45b与缺血性中风后的SVZ神经发生有关，并且Gadd45b通过BDNF介导缺血性中风后的大鼠SVZ中EE诱导的神经发生。这些结果表明，Gadd45b可能是增强脑缺血后成人神经发生的潜在治疗靶标。伴有脑源性神经营养因子（BDNF）的低表达。缺血性中风后的EE治疗上调SVZ中的Gadd45b和BDNF表达并增加神经发生。Gadd45b的抑制作用明显改善了EE诱导的神经发生增加。这些数据表明，Gadd45b与缺血性中风后的SVZ神经发生有关，并且Gadd45b通过BDNF介导缺血性中风后的大鼠SVZ中EE诱导的神经发生。这些结果表明，Gadd45b可能是增强脑缺血后成人神经发生的潜在治疗靶标。伴有脑源性神经营养因子（BDNF）的低表达。缺血性中风后的EE治疗上调SVZ中的Gadd45b和BDNF表达并增加神经发生。Gadd45b的抑制作用明显改善了EE诱导的神经发生增加。这些数据表明，Gadd45b与缺血性中风后的SVZ神经发生有关，并且Gadd45b通过BDNF介导缺血性中风后的大鼠SVZ中EE诱导的神经发生。这些结果表明，Gadd45b可能是增强脑缺血后成人神经发生的潜在治疗靶标。Gadd45b的抑制作用明显改善了EE诱导的神经发生增加。这些数据表明，Gadd45b与缺血性中风后的SVZ神经发生有关，并且Gadd45b通过BDNF在缺血性中风后的大鼠SVZ中介导EE诱导的神经发生。这些结果表明，Gadd45b可能是增强脑缺血后成人神经发生的潜在治疗靶标。Gadd45b的抑制作用明显改善了EE诱导的神经发生增加。这些数据表明，Gadd45b与缺血性中风后的SVZ神经发生有关，并且Gadd45b通过BDNF介导缺血性中风后的大鼠SVZ中EE诱导的神经发生。这些结果表明，Gadd45b可能是增强脑缺血后成人神经发生的潜在治疗靶标。