Pulsed Electromagnetic Fields Stimulate HIF-1α-Independent VEGF Release in 1321N1 Human Astrocytes Protecting Neuron-like SH-SY5Y Cells from Oxygen-Glucose Deprivation

Abstract

Pulsed electromagnetic fields (PEMFs) are emerging as an innovative, non-invasive therapeutic option in different pathological conditions of the central nervous system, including cerebral ischemia. This study aimed to investigate the mechanism of action of PEMFs in an in vitro model of human astrocytes, which play a key role in the events that occur following ischemia. 1321N1 cells were exposed to PEMFs or hypoxic conditions and the release of relevant neurotrophic and angiogenic factors, such as VEGF, EPO, and TGF-β1, was evaluated by means of ELISA or AlphaLISA assays. The involvement of the transcription factor HIF-1α was studied by using the specific inhibitor chetomin and its expression was measured by flow cytometry. PEMF exposure induced a time-dependent, HIF-1α-independent release of VEGF from 1321N1 cells. Astrocyte conditioned medium derived from PEMF-exposed astrocytes significantly reduced the oxygen-glucose deprivation-induced cell proliferation and viability decrease in the neuron-like cells SH-SY5Y. These findings contribute to our understanding of PEMFs action in neuropathological conditions and further corroborate their therapeutic potential in cerebral ischemia.

Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke

“…Furthermore, its effect has been proved in many cell types of the neurovascular unit. In this context, most in vitro studies are focused on neurons and microglia ( Vincenzi et al, 2017 ; Gessi et al, 2019 ; Merighi et al, 2020 ) and to a lesser extent on endothelial cells ( Font et al, 2019 ) and astrocytes ( Vincenzi et al, 2020 ). No studies have been reported analyzing the effect of PEMF on oligodendrocytes and pericytes which are also part of the neurovascular unit.…”

“…Even though in Vincenzi’s study astrocyte cultured media did not affect viability in neuron cells under OGD conditions ( Vincenzi et al, 2020 ), other authors have proven that OGD-astrocyte conditioned media alone could augment neuronal death ( Jin et al, 2017 ) and decrease microglia cell death ( Redzic et al, 2015 ). Thus, EMF experiments where culture media is collected in cell cultures subjected to OGD or other stimuli mimicking the ischemic processes should also be performed because all cell types of the neurovascular units are affected after a stroke.…”

“…A series of in vitro studies have been done using a PEMF of 1.5 mT, 75 Hz ( Cadossi et al, 1992 ), focusing on different cell types and ischemic models ( Vincenzi et al, 2017 , 2020 ; Gessi et al, 2019 ; Merighi et al, 2020 ). PEMF attenuated inflammation and hypoxia-induced injury using different cell lines (human neuroblastoma-derived SH-SY5Y cells, rat pheochromocytoma PC12 cells, and N9 microglial cells) ( Vincenzi et al, 2017 ).…”

“…Complementing the beneficial effects of PEMF induced in microglia, PEMF triggered protective actions in astrocytes ( Vincenzi et al, 2020 ). PEMF exposure increased vascular endothelial growth factor (VEGF ) released in 1321N1 astrocytes in a time dependent manner, with a maximum effect at 24 h (3.2-fold vs. normoxia).…”

“…However, it should be noticed that PEMF-stimulated astrocytes were not subjected to ischemic conditions. It seems logical to postulate that if hypoxia and EMF separately increase VEGF ( Vincenzi et al, 2020 ), then their combined actions should lead to a greater increase in VEGF. However, previous results have demonstrated different effects of EMF in the presence or absence of an ischemic scenario ( Rauš et al, 2013 ).…”