Figure 2

Activated microglia and the redistribution of ion channels can potentiate axonal injury during MS. Activated microglia can be a source of nitric oxide (NO), glutamate (Glut) or various proteases. Released free radicals, excitotoxic glutamate and various proteases can damage axonal mitochondria, leading to an imbalance in the energy demands/supply of axons. This along with the increased voltage-gated sodium channels (Na_v) dispersed along denuded axons, can potentiate persistent Na⁺ influx. To compensate for this redistribution, increased expression of the Na⁺/Ca²⁺ exchanger functions in reverse, thereby cytotoxic levels of Ca²⁺ can mediate axonopathy.