Lentiviral Vector-Mediated p27kip1 Expression Facilitates Recovery After Spinal Cord Injury
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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.
KeywordsSpinal cord injury p27kip1 Apoptosis Proliferation Cell cycle
Spinal cord injury
Cyclin-dependent kinase inhibitors
Phosphorylated retinoblastoma protein
Basso, Beattie, and Bresnahan scale
Combined behavioral score
Proliferating cell nuclear antigen
Neuronal nuclear antigen
Glial fibrillary acidic protein
Ionized calcium-binding adapter molecule 1
Myelin basic protein
This work was supported by the National Natural Science Foundation of China (No. 81171140, No. 81471258, No. 31300902), the Colleges and Universities in Natural Science Research Project of Jiangsu Province (13KJB310009), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Compliance with Ethical Standards
All surgical interventions and postoperative animal care were carried out in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996, USA) and were approved by the Chinese National Committee to the Use of Experimental Animals for Medical Purposes, Jiangsu Branch. All efforts were made to minimize the number of animals used and their suffering.
Conflict of Interests
The authors declare that they have no competing interests.
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