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Interactions between glia and electromagnetic fields in neurological disorders and regeneration of the central nervous system

Neurological diseases are a great burden for patients. They also represent a financial problem for the society. Since the cost of annual medical care for people with neurological diseases in the European Union alone has reached 800 billion EUR, there is a great need for new therapeutic approaches. Although there are available drugs on the market which alleviate the symptoms of neurodegenerative, neuroimmune and neurovascular diseases, they are not selective. At the same time, they represent a great cost to public health institutions. Therefore, it is very important to discover the molecular mechanisms that form the basis of the origin and progression of these diseases. Thus, novel treatment strategies should be discovered and proposed. For that purpose, this work is focused on elucidating the significance of electromagnetic fields, both innate and external, on neural disease etiology and therapy, respectively. Since electromagnetic fields can affect electrically charged cells located in their vicinity, they can influence the activity of neurons and glial cells and, with that, play a role in furthering tissue damage or initiate neuroregeneration. Using advanced mathematical modeling, the nature of innate inhomogeneous time-varying electromagnetic fields around axons was described first. Secondly, an update to the Hodgkin-Huxley model to include transverse and longitudinal current flow and qualification of the induced fields around neurons through modification of inhomogeneous forms of Maxwell’s equations was made. The nature of the field is conditioned by the proper function of neurons. If there is a degeneration or demyelination of the tissue, the nature of the fields that arise during the expansion of the action potential changes. This change is reflected in the function of the surrounding cells. Furthermore, during the neuroinflammation that accompanies neurodegeneration, cells of the adaptive immune system infiltrate the central nervous system. These cells can mistakenly “recognize” the altered field around the axon as a microorganism and initiate an immune response. This could be the backbone for occurrence of many diseases s with unknown or not well explored etiology. Thirdly, the presumed influence of electromagnetic fields on glial cells and neurons was described, using extensive review of the existing literature. This was followed by predicting their potential role in disease etiology and development as well as nerve tissue regeneration. Starting from the idea that the main molecular targets for electromagnetic field application are heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+) and hypoxia inducible factor 1α (HIF1α), it was postulated that, through acting on these molecular mediators, external 113 electromagnetic fields induce the alternative activation pathways in microglia (M2) and astrocytes (A2). A protective role and initiation of glial scar formation and subsequent neuroregeneration may be beneficial consequences of these processes. On the other hand, because of their inhomogeneous nature, innate electromagnetic fields around neurons are thought to induce the classically activated microglia (M1) and astrocyte (A1) pathway, leading to further worsening of the injury, on overactive immune response and further tissue degeneration. This research is a pioneering work trying to define the presence of innate inhomogeneous electromagnetic fields around axons and explain their importance in physiological and pathological processes within the central nervous system. Based on the model here, it is possible to design an instrument that could influence the innate fields within the nervous system and, consequentially, the process of neuroinflammation. This innovative concept could lead to a new approach to the treatment of diseases with an inflammatory or degenerative component and suggest alternative methods of glial cell activation in neurological diseases

electromagnetic fields, CNS, microglia, astrocytes, inflammation

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