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  3. Conditional ablation of reactive astrocytes to dissect their roles in spinal cord injury and repair

Conditional ablation of reactive astrocytes to dissect their roles in spinal cord injury and repair

  • Brain Behav Immun. 2019 Aug;80:394-405. doi: 10.1016/j.bbi.2019.04.016.
Yakun Gu 1,  Xueyan Cheng 1,  Xiao Huang 2,  Yimin Yuan 2,  Shangyao Qin 2,  Zijian Tan 2,  Dan Wang 2,  Xin Hu 3,  Cheng He 4,  Zhida Su 5
Affiliations

Affiliations

  • 1 Center for Brain Disorders Research, Capital Medical University, Center of NeuralInjury and Repair, Beijing Institute for Brain Disorders, Beijing, China; Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, China.
  • 2 Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, China.
  • 3 Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, China; Department of Neurological Surgery, Xixi Hospital of Hangzhou, Hangzhou, China.
  • 4 Center for Brain Disorders Research, Capital Medical University, Center of NeuralInjury and Repair, Beijing Institute for Brain Disorders, Beijing, China; Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, China. Electronic address: [email protected].
  • 5 Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, Shanghai, China. Electronic address: [email protected].
PMID: 30959174 DOI: 10.1016/j.bbi.2019.04.016
Abstract

Astrocytes become reactive in response to spinal cord injury (SCI) and ultimately form a histologically apparent glial scar at the lesion site. It is controversial whether astrocytic scar is detrimental or beneficial to the axonal regeneration and SCI repair. Therefore, much effort has focused on understanding the functions of reactive astrocytes. Here, we used a lentivirus-mediated herpes simplex thymidine kinase/ganciclovir (HSVtk/GCV) system to selectively kill scar-forming reactive proliferating astrocytes. The suicide gene expression was regulated by human glial fibrillary acidic protein (hGFAP) promoter, which is active primarily in astrocytes. Conditional ablation of reactive astrocytes in a mouse SCI model with crush injury impeded glial scar formation and resulted in widespread infiltration of inflammatory cells, increased neuronal loss, and severe tissue degeneration, which ultimately led to the failure of spontaneous functional recovery. These results suggest that reactive proliferating astrocytes play key roles in the healing process after SCI, shedding LIGHT on the potential benefit for the repair after central nervous system (CNS) injury.

Keywords

Astrocytes; Conditional ablation; Neural repair; Neuroinflammation; Spinal cord injury; Suicide gene.

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