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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

Jian Li, Zhiqiang Jia, Wen Xu, Weidong Guo, Mingchao Zhang, Jing Bi, Yang Cao, Zhongkai Fan, Gang Li

Life Sci. 2019 Apr 1;222:148-157.

PMID: 30851336

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP51987996	TGN-020		51987-99-6	Price

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