中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 769-779.doi: 10.4103/NRR.NRR-D-24-01491

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Sox2过表达的神经干细胞可有效改善出血后脑积水的脑室扩大和神经功能障碍

  

  • 出版日期:2026-02-15 发布日期:2025-05-24

Sox2-overexpressing neural stem cells alleviate ventricular enlargement and neurological dysfunction in posthemorrhagic hydrocephalus

Baocheng Gao1, 2, #, Haoxiang Wang1, #, Shuang Hu3, #, Kunhong Zhong1 , Xiaoyin Liu1 , Ziang Deng1 , Yuanyou Li1 , Aiping Tong4, *, Liangxue Zhou1, 5, 6, *   

  1. 1 Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;  2 Department of Neurosurgery, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China;  3 Department of Otolaryngology & Head and Neck Surgery, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, China;  4 State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Chengdu, Sichuan Province, China;  5 Department of Neurosurgery, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital),School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan Province, China;  6 Department of Neurosurgery, Fifth People’s Hospital of Ningxia Hui Autonomous Region, Shizuishan, Ningxia Hui Autonomous Region, China
  • Online:2026-02-15 Published:2025-05-24
  • Contact: Liangxue Zhou, MD, PhD, zhlxlll@163.com; Aiping Tong, MD, PhD, aipingtong@scu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82473334 (to LZ), 82401629 (to XL); the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region, No. 2022CJE09013 (to LZ); Mianyang Science and Technology Bureau (Mianyang Science and Technology Program), No. 2023ZYDF097 (to LZ); NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), No. 2023HYX001 (to LZ); Spinal Cord Diseases Clinical Medical Center of Yunnan Province, No. 2024JSKFKT-16 (to BG); the Natural Science Foundation of Sichuan Province, No. 2024NSFSC1646 (to XL); and the China Postdoctoral Science Foundation, Nos. GZC20231811 (to XL), 2024T170601 (to XL) and 2024M76228 (to XL).

摘要:

神经干细胞具有自我更新和多向分化的潜力,且对多种疾病有积极效果,但是出血性脑积水发生后,移植的神经干细胞在缺血缺氧的微环境中仅有1%-10%的干细胞能够存活。Sox2是神经干细胞维持增殖的重要因素。因此Sox2过表达的神经干细胞在理论上更能改善出血后脑积水后的神经功能障碍。此次实验将过表达Sox2的人源神经干细胞(NSCSox2)移植到出血性脑积水小鼠模型中,同时给予维甲酸进一步促进神经干细胞分化。结果显示,NSCSox2移植可明显缩小出血性脑积水引起的脑室扩大,同时改善出血性脑积水导致的神经功能障碍。NSCSox2还可促进神经再生,同时能明显抑制神经炎症反应,并能促进激活的小胶质细胞更多的向抑炎表型(M2表型)转化,从而减轻脉络丛炎症导致的脑脊液分泌。上述结果表明,NSCSox2移植可通过促进神经再生和调节炎症减轻出血后脑积水后脑室扩大及神经功能障碍。

https://orcid.org/0000-0001-9991-6358 (Liangxue Zhou); https://orcid.org/0000-0002-3392-5443 (Aiping Tong)

关键词: 神经干细胞, Sox2, 维甲酸, 出血后脑积水, 海马移植, 脑脊液, 神经发生, 血管生成, 小胶质细胞, 炎症

Abstract: Neural stem cells (NSCs) have the potential for self-renewal and multidirectional differentiation, and their transplantation has achieved good efficacy in a variety of diseases. However, only 1%–10% of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus. Sox2 is an important factor for NSCs to maintain proliferation. Therefore, Sox2-overexpressing NSCs (NSCSox2) may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus. In this study, human NSCSox2 was transplanted into a posthemorrhagic hydrocephalus mouse model, and retinoic acid was administered to further promote NSC differentiation. The results showed that NSCSox2 attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function. NSCSox2 also promoted nerve regeneration, inhibited neuroinflammation and promoted M2 polarization (antiinflammatory phenotype), thereby reducing cerebrospinal fluid secretion in choroid plexus. These findings suggest that NSCSox2 rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.

Key words: angiogenesis, cerebrospinal fluid, hippocampal transplantation, inflammation, microglia, neural stem cells, neurogenesis, posthemorrhagic hydrocephalus, retinoic acid, Sox2