Figure 1.

MeHg-mediated axonal degeneration is caused by a neurite outgrowth/contraction imbalance, and the effects are reversed by fasudil treatment. There are two mechanisms behind the therapeutic effect of fasudil on MeHg-induced neurodegeneration in the subacute phase (A) and in the chronic phase (B) in a MeHg-intoxicated rat model. (A) MeHg-induced downregulation of Rac1 causes a neurite outgrowth/contraction imbalance and axonal degeneration. ROCK2 inhibition by fasudil modifies the neurite outgrowth/contraction imbalance and protects cortical neurons from axonal degeneration and apoptotic neuronal cell death. (B) Fasudil suppresses the ROCK1 activity of invaded microglia, followed by downregulation of pro-inflammatory factors, including TNFα, iNOS, IL-1β, and IL-6, and upregulation of the anti-inflammatory factors arginase1 and IL-10. The Rho/ROCK pathway of microglia is essential for the chronic phase of MeHg-induced cerebrocortical neurodegeneration.