ROCK Inhibition with Fasudil Promotes Early Functional Recovery of Spinal Cord Injury in Rats by Enhancing Microglia Phagocytosis

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 36; no. 1; pp. 31 - 36
• Main Author: 付佩彩 唐荣华 万跃 谢敏杰 王伟 骆翔 喻志源
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.02.2016; Key Laboratory of Neurological Diseases of Huazhong University of Science and Technology,Ministry of Education of China,Wuhan 430030,China; Department of Neurology,Tongji Hospital Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China%Department of Neurology,the Third People's Hospital of Hubei Province,Wuhan 430030,China%Department of Neurology,Tongji Hospital Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use; Animals; Apoptosis; Male; Medicine; Medicine & Public Health; Microglia - drug effects; Microglia - metabolism; Myelin Basic Protein - metabolism; Myelin Sheath - metabolism; Phagocytosis; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Spinal Cord Injuries - drug therapy; 临床; 医学; 症状; 诊断; spinal cord injury; phagocytosis; Rho/ROCK; microglia
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-016-1537-3

Emerging evidence indicates that microglia activation plays an important role in spinal cord injury（SCI） caused by trauma. Studies have found that inhibiting the Rho/Rho-associated protein kinase（ROCK） signaling pathway can reduce inflammatory cytokine production by microglia. In this study, Western blotting was conducted to detect ROCK2 expression after the SCI; the ROCK Activity Assay kit was used for assay of ROCK pathway activity; microglia morphology was examined using the CD11 b antibody; electron microscopy was used to detect microglia phagocytosis; TUNEL was used to detect tissue cell apoptosis; myelin staining was performed using an antibody against myelin basic protein（MBP）; behavioral outcomes were evaluated according to the methods of Basso, Beattie, and Bresnahan（BBB）. We observed an increase in ROCK activity and microglial activation after SCI. The microglia became larger and rounder and contained myelin-like substances. Furthermore, treatment with fasudil inhibited neuronal cells apoptosis, alleviated demyelination and the formation of cavities, and improved motor recovery. The experimental evidence reveals that the ROCK inhibitor fasudil can regulate microglial activation, promote cell phagocytosis, and improve the SCI microenvironment to promote SCI repair. Thus, fasudil may be useful for the treatment of SCI.