The hippocampus is implicated in the generation of memory and learning, processes which involve extensive neuroplasticity. The generation of hippocampal adult-born neurons is particularly regulated by glial cells of the neurogenic niche and the surrounding microenvironment. Interestingly, recent evidence has shown that spinal cord injury (SCI) in rodents leads to hippocampal neuroinflammation, neurogenesis reduction, and cognitive impairments. In this scenario, the aim of this work was to evaluate whether an adenoviral vector expressing IGF1 could reverse hippocampal alterations and cognitive deficits after chronic SCI. SCI caused neurogenesis reduction and impairments of both recognition and working memories. We also found that SCI increased the number of hypertrophic arginase-1 negative microglia concomitant with the decrease of the number of ramified surveillance microglia in the hilus, molecular layer, and subgranular zone of the dentate gyrus. RAd-IGF1 treatment restored neurogenesis and improved recognition and working memory impairments. In addition, RAd-IGF1 gene therapy modulated differentially hippocampal regions. In the hilus and molecular layer, IGF1 gene therapy recovered the number of surveillance microglia coincident with a reduction of hypertrophic microglia cell number. However, in the neurogenic niche, IGF1 reduced the number of ramified microglia and increased the number of hypertrophic microglia, which as a whole expressed arginase-1. In summary, RAd-IGF1 gene therapy might surge as a new therapeutic strategy for patients with hippocampal microglial alterations and cognitive deficits such as those with spinal cord injury and other neurodegenerative diseases.

海马体与记忆和学习的产生有关，这些过程涉及广泛的神经可塑性。海马成年出生神经元的产生特别受神经原生态位的神经胶质细胞和周围微环境的调节。有趣的是，最近的证据表明，啮齿动物的脊髓损伤 (SCI) 会导致海马神经炎症、神经发生减少和认知障碍。在这种情况下，这项工作的目的是评估表达 IGF1 的腺病毒载体是否可以逆转慢性 SCI 后的海马改变和认知缺陷。SCI 导致神经发生减少以及识别和工作记忆的损害。我们还发现，SCI 增加了肥大精氨酸酶 1 阴性小胶质细胞的数量，同时伴随着齿状回的门、分子层和颗粒下区分支监视小胶质细胞数量的减少。RAd-IGF1 治疗恢复了神经发生并改善了识别和工作记忆障碍。此外，RAd-IGF1 基因治疗可调节不同的海马区域。在门和分子层，IGF1 基因治疗恢复了监测小胶质细胞的数量，同时减少了肥大的小胶质细胞数量。然而，在神经源性生态位中，IGF1 减少了分支小胶质细胞的数量并增加了肥大小胶质细胞的数量，这些小胶质细胞作为一个整体表达了 arginase-1。总之，