Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury
Autor: | Yan Zhang, Xiaohong Kong, Chenxi Zhao, Huiquan Duan, Bo Li, Baoyou Fan, Hongyu Shi, Qiu-Li Wu, Xue Yao, Shiqing Feng, Xin-Fu Zhou, Chao Sun |
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Přispěvatelé: | Duan, Hui Quan, Wu, Qiu-Li, Yao, Xue, Fan, Bao-You, Shi, Hong-Yu, Zhao, Chen-Xi, Zhang, Yan, Li, Bo, Sun, Chao, Kong, Xiao-Hong, Zhou, Xin-Fu, Feng, Shi-Qing |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
H&E stain Apoptosis Pharmacology Motor Activity nafamostat mesilate Neuroprotection Guanidines Luxol fast blue stain Proinflammatory cytokine neuroinflammation 03 medical and health sciences Random Allocation 0302 clinical medicine Thrombin Physiology (medical) medicine Animals Pharmacology (medical) Rats Wistar Spinal cord injury Neuroinflammation Spinal Cord Injuries Inflammation business.industry Anti-Inflammatory Agents Non-Steroidal apoptosis Original Articles Recovery of Function medicine.disease Spinal cord thrombin spinal cord injury Benzamidines Psychiatry and Mental health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents Spinal Cord Female business 030217 neurology & neurosurgery medicine.drug |
Popis: | Aim: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. Methods: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat. Hematoxylin and eosin staining (H & E staining) and Luxol fast blue (LFB) staining were used to observe the histological lesions. Apoptosis was examined by TUNEL staining, Annexin V-FITC/PI, caspase-3, and Bcl-2. Cytokines and neurotrophins were tested by Western blot. Locomotion recovery assessed by hindlimb BBB score and the inclined plane test. Results: Nafamostat mesilate treatment significantly improved locomotion recovery as assessed by hindlimb BBB scores and the inclined plane test. H & E staining and LFB staining showed a significant increase in spared tissue in both gray matter and white matter. NM decreased the expression of the proinflammatory cytokines TNF-α and IL-6. In addition, apoptosis was also significantly decreased, as shown by TUNEL staining and Annexin V-FITC/PI and by Western blotting for caspase-3 and Bcl-2 expression. Due to the mechanism of action of NM as a serine protease inhibitor, the drug decreased thrombin expression in the damaged spinal cord. Furthermore, NM increased the expression of neurotrophins (NT-3, BDNF, and NGF). Conclusions: Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury. Refereed/Peer-reviewed |
Databáze: | OpenAIRE |
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