Cinepazide maleate promotes recovery from spinal cord injury by inhibiting inflammation and prolonging neuronal survival

• Published in: Drug development research Vol. 84; no. 4; pp. 736 - 746
• Main Authors: Li, Dadi, Zhao, Shuxian, Zhu, Bin, Zhao, Wanmin, Ding, Ya, Li, Xuejun, Fu, Donglin, Yu, Haiyang, Wang, Baogui, Pan, Tan
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2023
• Subjects: Animals; Apoptosis; Cell culture; Cell injury; Cerebrospinal fluid; cinepazide maleate; DNA nucleotidylexotransferase; Functional testing; Hydrogen peroxide; In vivo methods and tests; Inflammation; Inflammation - metabolism; Injury prevention; Interleukin 6; Interleukin-6 - metabolism; Microglia; Rats; Rats, Sprague-Dawley; Recovery; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - drug therapy; spinal cord injury; Staining; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; spinal cord injury; apoptosis; inflammation; cinepazide maleate
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.22052

This study aimed to investigate the therapeutic effects of cinepazide maleate (CM) on spinal cord injury (SCI) in rats, thereby providing an experimental basis for the use of CM as a preventative and therapeutic strategy for SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and western blot analysis were used to assess neural cell apoptosis. enzyme‐linked immunosorbent assay was used to analyze the expression of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α (TNF‐α) in spinal cord tissues and cerebrospinal fluid. CD68 staining and western blot analysis were used to investigate the effect of CM on microglia activation. The effects of CM on motor function and histological damage in rats after SCI were investigated using the Basso‐Beattie‐Bresnahan (BBB) score, footprint assay, hematoxylin and eosin staining, and NeuN staining. In vitro models of neuronal cell injury and microglial inflammation were developed to investigate the effects of CM on apoptosis and inflammation. Functional tests (BBB score and footprint test) revealed that CM‐treated rats had significantly improved motor function. In vivo CM treatment reduced the number of apoptotic cells at the site of injury. Similarly, in vitro CM treatment reduced H2O2‐induced neuronal apoptosis. In vivo CM treatment reduced the number of CD68‐positive microglia and the expression levels of TNF‐α, IL‐1β, and IL‐6. Similarly, in vitro CM treatment reduced LPS‐induced pro‐inflammatory cytokines in microglia. CM promotes the recovery of motor function by inhibiting SCI‐induced apoptosis and inflammatory responses and reducing the area of the post‐SCI cavity in rats. These findings indicate that CM is a potential drug worthy of translational studies for SCI treatment.