Pulsed electric fields stimulate microglial transmitter release of VEGF, IL-8 and GLP-1 and activate endothelial cells through paracrine signaling.

As action potentials propagate along an axon, pulsed extracellular electric fields (E-fields) are induced. We investigated the role of E-fields in activating microglia cells and affecting capillary function and found that E-fields control human microglia secretions in concert with purinergic factors. We generated E-fields by applying transcranial pulsed electromagnetic fields (T-PEMF) identical to those appearing outside neurons as action potentials propagate. T-PEMF alone enhanced mRNA synthesis for VEGF, IL-8, IL-6 and the proglucagon gene as well as the PC1/3 enzyme that cleaves the proglucagon protein to glucagon and GLP-1 proteins. We found that T-PEMF enhanced secretion from microglia of VEGF, IL-8 and GLP-1 proteins having angiogenic and proliferative profiles. Interestingly, T-PEMF and purinergic transmitters together enhanced secretions confirming synergy between their actions. ATP also induced nitric oxide (NO) syntheses in distinct locations in the nucleus and the mRNA synthesis for the responsible iNOS was reduced by T-PEMF. When the microglia-secretory fluid was added to brain endothelial cells we saw vivid Ca signaling and enhanced transcription of mRNA for IL-8 and VEGF. Our previous work shows that applying T-PEMF to the human brain provides up to 60% remission for patients with refractory depressions within 8 weeks and improvements for Parkinson patients. Thus, physiological E-fields activate microglia, work synergistically with neurotransmitters, and cause paracrine secretions which cause activation of capillaries. Application of these E-Fields is effective for treating refractory depressions and appear promising for treating neurodegenerative brain diseases.