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.
Microglia are immunocompetent cells in the central nervous system that take up tissue debris and pathogens.Rho-associated kinase(ROCK) has been identified as an important regulator of uptake, proliferation, secretion, and differentiation in a number of cell types. Although ROCK plays critical roles in the microglial secretion of inflammatory factors,migration, and morphology, its effects on microglial uptake activity have not been well characterized. In the present study,we found that treatment of BV2 microglia and primary microglia with the ROCK inhibitors Y27632 and fasudil increased uptake activity and was associated with morphological changes. Furthermore, western blots showed that this increase in uptake activity was mediated through the extracellular-signal-regulated kinase(ERK) signaling cascade, indicating the importance of ROCK in regulating microglial uptake activity.
Peicai FuRonghua TangZhiyuan YuCaihong LiXue ChenMinjie XieWei WangXiang Luo
