Following nerve injury @entity6536 drives microglial proliferation and XXXX via the @entity8047 /ERK pathway.

@entity8047 @entity470 @entity584 @entity1897 @entity56 @entity158 @entity1366 @entity6536 @entity9 @entity1722
Following @entity1897 microglia accumulate within the spinal cord and adopt a proinflammatory phenotype a process which contributes to the development of @entity9 . We have recently shown that @entity6536 , a growth factor released following nerve injury, activates @entity1722 , 3, and 4 receptors on microglia and stimulates proliferation, survival and chemotaxis of these cells. Here we studied the intracellular signaling pathways downstream of @entity6536 - @entity470 activation in microglial cells. We found that @entity6536 in vitro induced phosphorylation of @entity1366 and @entity584 without activating p38MAPK. Using specific kinase inhibitors we found that the mitogenic effect of @entity6536 on microglia was dependant on @entity8047 / @entity1366 pathway, the chemotactic effect was dependant on PI3K/ @entity584 signaling and survival was dependant on both pathways. Intrathecal treatment with @entity6536 was associated with microgliosis and development of mechanical and @entity158 related @entity56 which was dependant on @entity1366 phosphorylation in microglia. Spinal nerve ligation results in a robust microgliosis and sustained @entity1366 phosphorylation within these cells. This pathway is downstream of @entity6536 / @entity470 signaling since its blockade resulted in a significant reduction in microglial @entity1366 phosphorylation. Inhibition of the @entity8047 / @entity1366 pathway resulted in decreased spinal microgliosis and in reduced mechanical and @entity56 after @entity1897 . We conclude that @entity6536 released after nerve injury activates microglial @entity470 receptors which consequently stimulates the @entity8047 / @entity1366 pathway that drives microglial proliferation and contributes to the development of @entity9 .
