Lentiviral Vector-Mediated p27^sup kip1^ Expression Facilitates Recovery After Spinal Cord Injury

Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these change...

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Veröffentlicht in:Molecular neurobiology 2016-11, Vol.53 (9), p.6043
Hauptverfasser: Chen, Min-hao, Liu, Yong-hua, Xu, Hua, Xu, Da-wei, Wang, Cheng-niu, Wang, Yi, Duan, Cheng-wei, Zhou, Ying, Kan, Peng, Shen, Ai-guo, Wang, You-hua
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container_issue 9
container_start_page 6043
container_title Molecular neurobiology
container_volume 53
creator Chen, Min-hao
Liu, Yong-hua
Xu, Hua
Xu, Da-wei
Wang, Cheng-niu
Wang, Yi
Duan, Cheng-wei
Zhou, Ying
Kan, Peng
Shen, Ai-guo
Wang, You-hua
description Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27kip1 in the lesioned spinal cord of adult rat. Treatment with LV-p27kip1 significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27kip1 overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27kip1 to inhibit cell cycle pathways. Thus, the present study provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of SCI.
doi_str_mv 10.1007/s12035-015-9498-2
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Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27kip1 in the lesioned spinal cord of adult rat. Treatment with LV-p27kip1 significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27kip1 overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27kip1 to inhibit cell cycle pathways. 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subjects Apoptosis
Cell cycle
Cell growth
Neurobiology
Spinal cord injuries
title Lentiviral Vector-Mediated p27^sup kip1^ Expression Facilitates Recovery After Spinal Cord Injury
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