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  2. TGN-020 alleviates edema and inhibits astrocyte activation and glial scar formation after spinal cord compression injury in rats

TGN-020 alleviates edema and inhibits astrocyte activation and glial scar formation after spinal cord compression injury in rats

  • Life Sci. 2019 Apr 1;222:148-157. doi: 10.1016/j.lfs.2019.03.007.
Jian Li 1 Zhiqiang Jia 2 Wen Xu 3 Weidong Guo 1 Mingchao Zhang 1 Jing Bi 4 Yang Cao 1 Zhongkai Fan 5 Gang Li 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China.
  • 2 Department of Spinal Surgery, The Second Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, China.
  • 3 School of Nursing, Jinzhou Medical University, Jinzhou 121000, China.
  • 4 Department of Neurobiology, Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical University, Jinzhou 121000, China.
  • 5 Department of Orthopedics, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China. Electronic address: fanzk_ln@163.com.
  • 6 Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: ganglili@126.com.
Abstract

Aims: Identifying drugs that inhibit edema and glial scar formation and increase neuronal survival is crucial to improving outcomes after spinal cord injury (SCI). Here, we used 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a potent selective inhibitor of Aquaporin 4 (AQP4), to investigate the effects of TGN-020 on SCI in Sprague-Dawley rats.

Main methods: We compressed the spinal cord at T10 using a sterile impounder (35 g, 5 min), to induce moderate injury. TGN-020 (100 mg/kg) or an equal volume of 10% dimethyl sulfoxide was then administered via intraperitoneal injection. Neurological function was evaluated using the Basso-Beattie-Bresnahan open-field locomotor scale 1, 3, 7, 14, 21, and 28 days after SCI. The degree of edema was assessed via determination of the precise spinal cord water content 3 days after SCI. Expression levels of AQP4, glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA), and growth-associated protein-43 (GAP-43) were determined via western blotting and immunofluorescence staining 3 days after SCI and 4 weeks after SCI. Numbers of surviving neurons and glial scar sizes were determined using Nissl and hematoxylin-eosin staining, respectively.

Key findings: Our results showed that TGN-020 promoted functional recovery at days 3, 7, 14, 21, and 28, as well as reduced the degree of edema and inhibited the expression of AQP4, GFAP, PCNA at days 3 after SCI. Furthermore, observations 4 weeks after SCI revealed that TGN-020 inhibited the glial scar formation and upregulated GAP-43 expression.

Significance: TGN-020 can alleviate spinal cord edema, inhibit glial scar formation, and promote axonal regeneration, conferring beneficial effects on recovery in rats.

Keywords

Aquaporin 4; Edema; Glial scar; Spinal cord injury; TGN-020.

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