Fig. 2

Extracellular factors regulating microglia and macrophage reactivity in progressive MS. Many characteristic features of MS pathophysiology may lead to the microglia and macrophages reactivity. Accumulation of meningeal inflammation, including accumulation of B cells, T cells and macrophages, results in microglia and macrophages reactivity in the underlying cortex. Leakage of the BBB results in blood components such as fibrinogen leaking into the CNS. Once in the CNS, fibrinogen is converted to fibrin which acts as a potent stimulus of microglia and macrophages. Demyelination and death of iron-rich oligodendrocytes release excess iron into the extracellular space, which can in turn act as a stimulus for microglia and macrophages