Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?

Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers. In neuronal diseases such as multiple sclerosis, the conduction properties of axons are disturbed by the removal of the myelin sheath, leaving nerve cells at a higher risk of degenerating. In some cases, the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells. In any case, however, changes in the ion channel organization occur and may help to restore impulse conduction after demyelination. On the other hand, changes in ion channel distribution may increase the energy demand of axons, thereby increasing the probability of axonal degeneration. Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis. These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation. However, these treatments either affect the entire organism (pharmacological) or exert a very local effect (electrodes). Current results show that neuronal activity is a strong regulator of oligodendroglial development. To bridge the gap between global and very local treatments, non-invasive transcranial magnetic stimulation could be considered. Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals. In this review, we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons. Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations, repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration.