Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury
Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury (TBI). Treatment options, including cell transplantation and drug therapy, have been shown to benefit TBI, although the underlying mechanisms remain elusive. In this study, neural stem cells (NSCs...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-09-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022123 |
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| author | Liu Sujuan Tian Haili Niu Yanmei Yu Chunxia Xie Lingjian Jin Zhe Niu Wenyan Ren Jun Fu Li Yao Zhi |
| author_facet | Liu Sujuan Tian Haili Niu Yanmei Yu Chunxia Xie Lingjian Jin Zhe Niu Wenyan Ren Jun Fu Li Yao Zhi |
| author_sort | Liu Sujuan |
| collection | DOAJ |
| description | Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury (TBI). Treatment options, including cell transplantation and drug therapy, have been shown to benefit TBI, although the underlying mechanisms remain elusive. In this study, neural stem cells (NSCs) are transplanted into TBI-challenged mice, together with olfactory ensheathing cells (OECs) or followed by valproic acid (VPA) treatment. Both OEC grafting and VPA treatment facilitate the differentiation of NSCs into neurons (including endogenous and exogenous neurons) and significantly attenuate neurological functional defects in TBI mice. Combination of NSCs with OECs or VPA administration leads to overt improvement in axonal regeneration, synaptogenesis, and synaptic plasticity in the cerebral cortex in TBI-challenged mice, as shown by retrograde corticospinal tract tracing, electron microscopy, growth-associated protein 43 (GAP43), and synaptophysin (SYN) analyses. However, these beneficial effects of VPA are reversed by local delivery of N-methyl-D-aspartate (NMDA) into tissues surrounding the injury epicenter in the cerebral cortex, accompanied by a pronounced drop in axons and synapses in the brain. Our findings reveal that increased axonal regeneration and synaptogenesis evoked by cell grafting and VPA fosters neural repair in a murine model of TBI. Moreover, VPA-induced neuroprotective roles are antagonized by exogenous NMDA administration and its concomitant decrease in the number of neurons of local brain, indicating that increased neurons induced by VPA treatment mediate axonal regeneration and synaptogenesis in mice after TBI operation. Collectively, this study provides new insights into NSC transplantation therapy for TBI. |
| first_indexed | 2024-03-11T12:21:06Z |
| format | Article |
| id | doaj.art-c1d6d6105094472abb00a8ee16a7b79c |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:21:06Z |
| publishDate | 2022-09-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-c1d6d6105094472abb00a8ee16a7b79c2023-11-07T01:01:35ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-09-01541289130010.3724/abbs.202212320d259ccCombined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injuryLiu Sujuan0Tian Haili1Niu Yanmei2Yu Chunxia3Xie Lingjian4Jin Zhe5Niu Wenyan6Ren Jun7Fu Li8Yao Zhi9["Department of Anatomy and Embryology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]["School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China"]["Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin 300070, China"]["Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]["Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]["Tianjin Yaohua Binhai School, Tianjin 300000, China"]["Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]["Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China","Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA"]["Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin 300070, China","Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]["Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China"]Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury (TBI). Treatment options, including cell transplantation and drug therapy, have been shown to benefit TBI, although the underlying mechanisms remain elusive. In this study, neural stem cells (NSCs) are transplanted into TBI-challenged mice, together with olfactory ensheathing cells (OECs) or followed by valproic acid (VPA) treatment. Both OEC grafting and VPA treatment facilitate the differentiation of NSCs into neurons (including endogenous and exogenous neurons) and significantly attenuate neurological functional defects in TBI mice. Combination of NSCs with OECs or VPA administration leads to overt improvement in axonal regeneration, synaptogenesis, and synaptic plasticity in the cerebral cortex in TBI-challenged mice, as shown by retrograde corticospinal tract tracing, electron microscopy, growth-associated protein 43 (GAP43), and synaptophysin (SYN) analyses. However, these beneficial effects of VPA are reversed by local delivery of N-methyl-D-aspartate (NMDA) into tissues surrounding the injury epicenter in the cerebral cortex, accompanied by a pronounced drop in axons and synapses in the brain. Our findings reveal that increased axonal regeneration and synaptogenesis evoked by cell grafting and VPA fosters neural repair in a murine model of TBI. Moreover, VPA-induced neuroprotective roles are antagonized by exogenous NMDA administration and its concomitant decrease in the number of neurons of local brain, indicating that increased neurons induced by VPA treatment mediate axonal regeneration and synaptogenesis in mice after TBI operation. Collectively, this study provides new insights into NSC transplantation therapy for TBI.https://www.sciengine.com/doi/10.3724/abbs.2022123traumatic brain injurytransplantationneural stem cellsvalproic acidN-methyl-D-aspartate |
| spellingShingle | Liu Sujuan Tian Haili Niu Yanmei Yu Chunxia Xie Lingjian Jin Zhe Niu Wenyan Ren Jun Fu Li Yao Zhi Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury Acta Biochimica et Biophysica Sinica traumatic brain injury transplantation neural stem cells valproic acid N-methyl-D-aspartate |
| title | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| title_full | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| title_fullStr | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| title_full_unstemmed | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| title_short | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| title_sort | combined cell grafting and vpa administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury |
| topic | traumatic brain injury transplantation neural stem cells valproic acid N-methyl-D-aspartate |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022123 |
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