Non-pulsed Sinusoidal Electromagnetic Field Rescues Animals From Severe Ischemic Stroke via NO Activation

I would expect immediate action from your doctors and stroke hospital to contact researchers and get human trials going.  Not really time dependent, 4 days for therapy. Or are there better ways to deliver nitric oxide?

• endothelial nitric oxide (1) 

• nitric oxide (94)

Non-pulsed Sinusoidal Electromagnetic Field Rescues Animals From Severe Ischemic Stroke via NO Activation

Lena P. Font^1,2, Miriam M. Cardonne², Hannelore Kemps¹, Raf Meesen¹, Oneida F. Salmon², Fidel G. González², Ivo Lambrichts¹, Jean-Michel Rigo¹, Bert Brône^1*† and Annelies Bronckaers^1*†

• ¹Faculty of Medicine and Life Sciences, BIOMED, UHasselt – Hasselt University, Diepenbeek, Belgium
• ²Centro Nacional de Electromagnetismo Aplicado, Universidad de Oriente, Santiago de Cuba, Cuba

Despite the high prevalence and devastating outcome, only a few treatment options for cerebral ischemic stroke exist. Based on the nitric oxide (NO)-stimulating capacity of Non-pulsed Sinusoidal Electromagnetic Field (NP-SEMF) and the possible neuroprotective role of NO in ischemic stroke, we hypothesized that NP-SEMF is able to enhance survival and neurological outcome in a rat model of cerebral ischemia. The animals, in which ischemic injury was induced by occlusion of both common carotid arteries, received 20 min of NP-SEMF of either 10 or 60 Hz daily for 4 days. NP-SEMF dramatically increased survival, reduced the size of the infarcted brain area and significantly improved the neurological score of the surviving rats. Corresponding to previous reports, NP-SEMF was able to induce NO production in vitro. The importance of NO as a key signaling molecule was highlighted by inhibition of the NP-SEMF beneficial effects in the rat stroke model after blocking NO synthase (NOS). Our results indicate for the first time that NP-SEMF exposure (13.5 mT at 60 and 10 Hz) improves the survival and neurological outcome of rats subjected to cerebral ischemia and that this effect is mediated by NO, underlining the great therapeutic potential of NP-SEMF as a therapy for ischemic stroke.

Introduction

Cerebral ischemic stroke is caused by the occlusion of a major artery in the brain, which results in extensive brain tissue loss. Cerebral ischemic stroke is a major cause of mortality and disability worldwide (Kissela et al., 2009; Feigin et al., 2014). Currently, the only available treatment options are tissue plasminogen activator and thrombectomy, which have significant effectivity after stroke. However, these therapies can only be used in a small subset of cases, indicating the clear need for new interventions (Zhang et al., 2013).

Nitric oxide (NO) is an important signaling molecule that is synthesized from its precursor L-arginine by nitric oxide synthase (NOS). Following stroke, NO produced by the neuronal and inducible isoforms of NOS exerts neurotoxic effects, while NO supplied by endothelial NOS (eNOS) is beneficial by stimulating several mechanisms such as vasodilation, angiogenesis, and neurogenesis. As a consequence of these later positive effects, NO donors display therapeutic effects in animal stroke models (Terpolilli et al., 2012; Garry et al., 2015). Extremely low frequency electromagnetic field () has been shown to induce NO production (Jelenkovic et al., 2006; Bragin et al., 2015). ELF-MF is defined by a magnetic flux below 20 mT with a frequency range of 1 to 300 Hz and is applied in a pulsed or non-pulsed fashion. Pulsed ELF-MF is intensively investigated and used in the clinic to treat delayed union bone fractures and wounds (Pesce et al., 2013). Furthermore, pulsed ELF-MF is beneficial in preclinical models of hind limb ischemia (Li et al., 2015), myocardial infarction (Yuan et al., 2010; Hao et al., 2014) and traumatic brain injury (Rasouli et al., 2012). In contrast, NP-SEMF is less studied but shows clinical promise in a rat model of Huntington’s disease (Tasset et al., 2012). Although the precise cellular mechanism activated by ELF-MF is poorly characterized, NO is induced by both pulsed ELF-MF and NP-SEMF in the brains of healthy rats (Jelenkovic et al., 2006; Bragin et al., 2015).

Because of the promising preclinical data of NO donors as a stroke therapy and the ability of NP-SEMF to induce NO production, we investigated the effect of NP-SEMF in a rat model of cerebral ischemia. We also studied the influence of NOS inhibition on NP-SEMF-induced neuroprotective effects. To our knowledge, this study is the first to show the therapeutic effect of NP-SEMF in brain ischemia and its NO-dependence.

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