Microglial activation/proliferation and reactive
astrogliosis are commonly observed and have been considered to be closely relevant
pathological processes during
spinal cord injury (SCI). However, the molecular mechanisms underlying this microglial-astroglial interaction are still poorly understood. We showed recently that the continuous injection of the cell cycle inhibitor
olomoucine not only markedly suppressed microglial proliferation and associated release of pro-inflammatory
cytokines, but also attenuated astroglial
scar formation and the lesion cavity and mitigated the functional deficits in rat SCI animal model. In this study, we asked whether microglial activation/proliferation plays an initial role and also necessary in maintaining
astrogliosis in SCI model. Our results showed that traumatic induced microglial activation/proliferation precedes
astrogliosis, and the up-regulated GFAP expression at both
mRNA and
protein levels was temporally posterior to the microglial activation. Furthermore, when the cell cycle inhibitor
olomoucine was administered only once 1 h post-SCI that should selectively suppress microglial proliferation, the subsequent SCI induced increase in GFAP expression at 1, 2 and 4 weeks was significantly attenuated, suggesting that microglial activation/proliferation played an important role for the later onset
astrogliosis after SCI. Consistent with the results that microglial proliferation always precedes astroglial proliferation and there is at present no evidence of other astroglial precursors, which as always does not mean that they will not be uncovered by further searching, and in view of the fact that microglial-derived pro-inflammatory
cytokines promote
astrogliosis as we reported recently, these findings together suggest that by release of
cytokines and other soluble products, the early onset microglial activation/proliferation can significantly influence the subsequent development of reactive
astrogliosis and
glial scar formation in SCI animal model.