Angiogenic effect of extremely low frequency magnetic field in experimental models of Cerebral Ischemia

Abstract

Cerebral vascular diseases (CVD) are positioned as the third leading cause of death and the leading cause of disability worldwide. They present a complex pathophysiology for which there is only one drug approved in the clinic: tissue plasminogen activator (tPA)203, which is only available for a small subset of patients. In this context, the search for new therapies is of the highest priority. The objective of the present study was to evaluate the neuroprotective effect of sinusoidal extremely low frequency magnetic field (ELFMFs) application in cerebral ischemia in various animal models, with particular emphasis on the angiogenesis process in vitro and in vivo. In the global ischemia model where occlusion of both carotids was induced in Wistar rats, ELFMFs significantly improved the survival rate and the neurological recovery and also reduced the ischemic lesion at the tested doses (13.5 mT / 10 and 60 Hz). In vitro, ELFMFs stimulate the proliferation, migration and tube formation, as well as the production of endothelial nitric oxide syntase (eNOS)-dependent NO, in in vitro HMEC-1 endothelial cell cultures. A significant increase in the number of blood vessels in the hippocampus region was observed after treatment with 13.5 mT / 60Hz, suggesting that the neuroprotective effect is mediated by angiogenesis. In addition, when the NOS-inhibitor L-NAME was co-administrated with ELFMF, the survival rate and infarction size was comparable to that of the untreated stroke animals, strongly suggesting that NO is the key signal molecule that mediates in the neuroprotective effect of ELFMF. Overall, the results indicate that ELFMF has a neuroprotective effect at preclinical level, which highlights its therapeutic potential of treatment for acute cerebral ischemia.