Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (2): 769-779.doi: 10.4103/NRR.NRR-D-24-01491

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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).

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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