Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammation.
Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI.
Su
Zhida
Z
Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
Yuan
Yimin
Y
Cao
Li
L
Zhu
Yanling
Y
Gao
Liang
L
Qiu
Yang
Y
He
Cheng
C
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D010616:Phenanthrenes / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology
D004224:Diterpenes; D004852:Epoxy Compounds; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D016900:Neurofilament Proteins; D010616:Phenanthrenes; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C001899:triptolide; C507927:Jak2 protein, rat; D053614:Janus Kinase 2