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Mol Neurobiol. 2016 Nov;53(9):6043-6056. doi: 10.1007/s12035-015-9498-2. Epub 2015 Nov 2.

Lentiviral Vector-Mediated p27kip1 Expression Facilitates Recovery After Spinal Cord Injury.

Author information

1
Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
2
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
3
Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
4
Basic Medical Research Centre, Medical School, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
5
Department of Medical Imaging, Medical School, Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
6
Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China. wangyouhua_nt@126.com.

Abstract

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.

KEYWORDS:

Apoptosis; Cell cycle; Proliferation; Spinal cord injury; p27kip1

PMID:
26526846
DOI:
10.1007/s12035-015-9498-2
[Indexed for MEDLINE]

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