中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (1): 141-155.doi: 10.4103/NRR.NRR-D-24-00802

• 综述:退行性病与再生 • 上一篇    下一篇

缺血性脑卒中后神经发生的增强：探索内源性和外源性干细胞之间的相互作用

  

  • 出版日期:2026-01-15 发布日期:2025-04-19
  • 基金资助:
    本研究得到了科技创新2030-“脑科学与类脑研究 ”重大项目，编号2022ZD0206200；国家自然科学基金，编号82371245，82102246，81701092；山东省自然科学基金，编号。82371245 , 82102246, 81701092；山东省自然科学基金，编号：ZR2020MH129；上海市临床重点专科，编号：shslczdzk03601；上海市围手术期器官支持与功能保护工程技术研究中心，编号：20DZ2254200。

Current understanding and prospects for targeting neurogenesis in the treatment of cognitive impairment

Ye Liu1, 2, 3, Xibing Ding1, 2, Shushan Jia3, *, Xiyao Gu1, 2, 3, *   

  1. 1 Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;  2 Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China;  3 Second School of Clinical Medicine of Binzhou Medical University, Yantai, Shandong Province, China
  • Online:2026-01-15 Published:2025-04-19
  • Contact: Shushan Jia, PhD, jiashushan@163.com; Xiyao Gu, PhD, gxykevin@126.com.
  • Supported by:
    This work was supported by Technological Innovation 2030-Major Projects of “Brain Science and Brain-like Research,” No. 2022ZD0206200 (to XG); the National Natural Science Foundation of China, No. 82371245 (to SJ), 82102246 (to XD), 81701092 (to XG); the Natural Science Foundation of Shandong Province, No. ZR2020MH129 (to SJ); Shanghai Municipal Key Clinical Specialty, No. shslczdzk03601; and Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation, No. 20DZ2254200

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摘要：

成人海马神经发生与成人大脑的记忆形成有关，与海马中的成熟神经元相比，新神经元在未成熟阶段表现出更大的可塑性。异常的成人海马神经发生与中枢神经系统疾病中的认知障碍密切相关。针对成人海马神经发生和调节神经发生已被证明可以改善认知障碍。文章旨在阐述目前对神经发生治疗认知障碍的认识和前景。最新研究表明，成人海马神经发生异常存在于多种认知障碍疾病中，包括脑血管疾病、阿尔茨海默病、衰老相关疾病以及与麻醉和手术相关的疾病。成人海马神经发生异常在这些疾病导致的认知障碍中的作用已得到广泛认可，针对成人海马神经发生的治疗被认为是治疗认知障碍的一种有前景的方法。然而，认知障碍发生成人海马神经发生异常的机制尚未完全明了，靶向成人海马神经发生治疗认知障碍的效果有限，治疗方法和检测技术也有待进一步发展。通过回顾近期的研究，文章将认知障碍异常的潜在机制归纳为4个方面：免疫、能量代谢、衰老和病理状态。在与免疫相关的机制中，脑膜免疫、脑免疫和外周免疫异常可导致成人海马神经发生异常。脂质代谢紊乱和线粒体代谢紊乱是能量代谢导致成人海马神经发生异常的主要因素。在衰老过程中，神经源龛的炎症状态和与衰老相关的microRNAs的表达是导致老年患者成人海马神经发生减少和认知障碍的机制。身体病理状态和情绪病理状态也是导致神经源龛异常的可能机制。在目前针对成人海马神经发生的策略中，运动、经皮神经电刺激和丰富的环境等物理治疗方法可有效改善成人海马神经发生。饮食干预，如限制能量摄入和改善营养状况，已在基础研究和临床试验中被证明有效。然而，药物治疗，如使用抗抑郁药和干细胞疗法，仍主要在基础研究中报道，临床研究参与有限。总之，成人海马神经发生异常与认知障碍之间的关系已受到广泛关注。值得注意的是，以成人海马神经发生为靶点可以成为治疗认知障碍的重要手段。然而，成人海马神经发生异常背后的机制尚不清楚，也缺乏有针对性的成人海马神经发生治疗方法，这凸显了将研究成果转化为临床实践的必要性。

https://orcid.org/0009-0007-8842-4316 (Shushan Jia); https://orcid.org/0000-0003-1203-9298 (Xiyao Gu)

关键词: 衰老, 阿尔茨海默病, 脑血管疾病, 认知障碍, 能量代谢, 海马, 免疫机制, 神经发生, 病理状态, 治疗

Abstract: Adult hippocampal neurogenesis is linked to memory formation in the adult brain, with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons. Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases. Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits. This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment. Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment, including cerebrovascular diseases, Alzheimer’s disease, aging-related conditions, and issues related to anesthesia and surgery. The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized, and targeting AHN is considered a promising approach for treating cognitive impairment. However, the underlying mechanisms of this role are not yet fully understood, and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited, with a need for further development of treatment methods and detection techniques. By reviewing recent studies, we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories: immunity, energy metabolism, aging, and pathological states. In immunity-related mechanisms, abnormalities in meningeal, brain, and peripheral immunity can disrupt normal adult hippocampal neurogenesis. Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis. During aging, the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients. Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis. Among the current strategies used to enhance this form of neurogenesis, physical therapies such as exercise, transcutaneous electrical nerve stimulation, and enriched environments have proven effective. Dietary interventions, including energy intake restriction and nutrient optimization, have shown efficacy in both basic research and clinical trials. However, drug treatments, such as antidepressants and stem cell therapy, are primarily reported in basic research, with limited clinical application. The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention, and targeting the former may be an important strategy for treating the latter. However, the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear, and treatments are lacking. This highlights the need for greater focus on translating research findings into clinical practice.

Key words: aging, Alzheimer’s disease, cerebrovascular diseases, cognitive impairment, energy metabolism, hippocampus, immune mechanisms, neurogenesis, pathological states, treatment