Molecular Neurobiology

, Volume 53, Issue 9, pp 6043–6056 | Cite as

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

  • Min-hao Chen
  • Yong-hua Liu
  • Hua Xu
  • Da-wei Xu
  • Cheng-niu Wang
  • Yi- Wang
  • Cheng-wei Duan
  • Ying Zhou
  • Peng Kan
  • Ai-guo Shen
  • You-hua Wang
Article

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

Spinal cord injury p27kip1 Apoptosis Proliferation Cell cycle 

Abbreviations

SCI

Spinal cord injury

CDKs

Cyclin-dependent kinases

CDKIs

Cyclin-dependent kinase inhibitors

pRb

Phosphorylated retinoblastoma protein

BBB

Basso, Beattie, and Bresnahan scale

CBS

Combined behavioral score

PCNA

Proliferating cell nuclear antigen

NeuN

Neuronal nuclear antigen

GFAP

Glial fibrillary acidic protein

IBa1

Ionized calcium-binding adapter molecule 1

MBP

Myelin basic protein

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Min-hao Chen
    • 1
  • Yong-hua Liu
    • 2
  • Hua Xu
    • 1
  • Da-wei Xu
    • 3
  • Cheng-niu Wang
    • 4
  • Yi- Wang
    • 5
  • Cheng-wei Duan
    • 2
  • Ying Zhou
    • 2
  • Peng Kan
    • 1
  • Ai-guo Shen
    • 2
  • You-hua Wang
    • 1
  1. 1.Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug TargetMedical College of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Jiangsu Province Key Laboratory for Inflammation and Molecular Drug TargetMedical College of Nantong UniversityNantongPeople’s Republic of China
  3. 3.Department of Orthopaedics, The Second Affiliated Hospital of Nantong UniversityNantong UniversityNantongPeople’s Republic of China
  4. 4.Basic Medical Research Centre, Medical SchoolNantong UniversityNantongPeople’s Republic of China
  5. 5.Department of Medical Imaging, Medical SchoolNantong UniversityNantongPeople’s Republic of China

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