Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 80, Issue -, Pages 394-405Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2019.04.016
Keywords
Astrocytes; Suicide gene; Conditional ablation; Spinal cord injury; Neuroinflammation; Neural repair
Categories
Funding
- National Natural Science Foundation [31671110]
- National Key Research and Development Program of China [2016YFA0100802]
- Fund from Navy Medical University [2016JS03]
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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.
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