ROCK inhibition with fasudil promotes early functional recovery of spinal cord injury in rats by enhancing microglia phagocytosis

Summary

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 CD11b 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.

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Correspondence to Zhi-yuan Yu 喻志源.

Additional information

This project was supported by grants from Natural Science Foundation of China (No. 81471200 and No. 81000521), National Basic Research Program of China (No. 2011CB504403) and the Young Medical Scientists Project of Wuhan (No. 2013-12).

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Fu, Pc., Tang, Rh., Wan, Y. et al. ROCK inhibition with fasudil promotes early functional recovery of spinal cord injury in rats by enhancing microglia phagocytosis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 31–36 (2016). https://doi.org/10.1007/s11596-016-1537-3

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Key words

  • Rho/ROCK
  • microglia
  • spinal cord injury
  • phagocytosis