PMID- 36988113 OWN - NLM STAT- MEDLINE DCOM- 20230612 LR - 20231116 IS - 1098-2299 (Electronic) IS - 0272-4391 (Linking) VI - 84 IP - 4 DP - 2023 Jun TI - Cinepazide maleate promotes recovery from spinal cord injury by inhibiting inflammation and prolonging neuronal survival. PG - 736-746 LID - 10.1002/ddr.22052 [doi] AB - 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)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) 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 H(2) O(2) -induced neuronal apoptosis. In vivo CM treatment reduced the number of CD68-positive microglia and the expression levels of TNF-alpha, IL-1beta, 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. CI - (c) 2023 Wiley Periodicals LLC. FAU - Li, Dadi AU - Li D AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Zhao, Shuxian AU - Zhao S AD - Department of Infectious Disease, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Zhu, Bin AU - Zhu B AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Zhao, Wanmin AU - Zhao W AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Ding, Ya AU - Ding Y AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Li, Xuejun AU - Li X AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Fu, Donglin AU - Fu D AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Yu, Haiyang AU - Yu H AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Wang, Baogui AU - Wang B AD - Department of Infectious Disease, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. FAU - Pan, Tan AU - Pan T AUID- ORCID: 0009-0009-1760-6803 AD - Department of Orthopedics, The Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang People's Hospital, Fuyang, Anhui, China. LA - eng GR - Health Commission of Anhui province (AHWJ2021b111), Health Commission of Fuyang City (FY2021-002), Anhui Medical University Fund project (2021xkj210), and Key Project of natural sciences in Bengbu Medical College (2022byzd165)./ PT - Journal Article DEP - 20230329 PL - United States TA - Drug Dev Res JT - Drug development research JID - 8204468 RN - 67Y4P5C84X (cinepazide) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-6) SB - IM MH - Rats MH - Animals MH - Rats, Sprague-Dawley MH - *Tumor Necrosis Factor-alpha/metabolism MH - Interleukin-6/metabolism MH - *Spinal Cord Injuries/drug therapy MH - Spinal Cord/metabolism/pathology MH - Inflammation/metabolism MH - Apoptosis OTO - NOTNLM OT - apoptosis OT - cinepazide maleate OT - inflammation OT - spinal cord injury EDAT- 2023/03/30 06:00 MHDA- 2023/06/12 06:43 CRDT- 2023/03/29 07:03 PHST- 2023/03/03 00:00 [revised] PHST- 2023/01/08 00:00 [received] PHST- 2023/03/13 00:00 [accepted] PHST- 2023/06/12 06:43 [medline] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/29 07:03 [entrez] AID - 10.1002/ddr.22052 [doi] PST - ppublish SO - Drug Dev Res. 2023 Jun;84(4):736-746. doi: 10.1002/ddr.22052. Epub 2023 Mar 29.