摘要
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(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
基金
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)
the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
