Pulsed Electromagnetic Fields: A Novel Attractive Therapeutic Opportunity for Neuroprotection After Acute Cerebral Ischemia

Author: Fioravante Capone1, Simona Salati2, Fabrizio Vincenzi3, Micaela Liberti4, Giorgio Aicardi5, Francesca Apollonio4, Katia Varani3, Ruggero Cadossi2, Vincenzo Di Lazzaro1
Affiliation: <sup>1</sup> Unit of Neurology, Neurophysiology, and Neurobiology, Department of Medicine, Università Campus Bio-Medico, Roma, Italy. <sup>2</sup> IGEA SpA, Clinical Biophysics, Carpi, Italy. <sup>3</sup> Department of Translational Medicine, University of Ferrara, Italy. <sup>4</sup> Department of Information Engineering, Electronics and Telecommunications (DIET), University of Rome &quot;La Sapienza&quot;, Roma, Italy. <sup>5</sup> Neurophysiology Research Unit, Department for Life Quality Studies, University of Bologna, Bologna, Italy.
Conference/Journal: Neuromodulation
Date published: 2021 Sep 4
Other: Special Notes: doi: 10.1111/ner.13489. , Word Count: 274

Acute cerebral ischemia is characterized by several pathological processes evolving during time, which contribute to the final tissue damage. Secondary processes, such as prolonged inflammatory response, impaired mitochondrial function and oxidative stress, are responsible for the progression of brain injury to the peri-infarct area, called "penumbra." Adenosine has been shown to play a crucial role in regulating the inflammatory cascade following brain ischemia. Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors, increasing the functionality of the endogenous adenosine. In particular, PEMF exposure induces a significant upregulation of A2A and A3 adenosine receptors in different neuronal cell types. Several lines of evidence suggest that PEMF exposure might play a neuroprotective role after ischemic damage.

Materials and methods:
This review summarizes the current knowledge on the mechanism of action of PEMFs and their biological effects on neuronal damage both in preclinical and clinical studies.

PEMFs counteract hypoxia-induced apoptosis and ROS production in neuronal-like cells and exert a strong anti-inflammatory effect on microglial cells. Data from stroke animal models showed that PEMFs exposure is able to reduce the size of the infarct area and decrease the levels of pro-inflammatory mediators. In clinical studies, PEMFs stimulation proved to be safe and well tolerated. Preliminary results on acute ischemic stroke patients showed a dose-dependent reduction in the lesion size.

Altogether, these data demonstrate the efficacy of PEMFs against several mechanisms underlying ischemic damage and suggest that PEMFs might represent a novel noninvasive adjunctive treatment for acute ischemic stroke, providing neuroprotection and reducing functional deficits following ischemia.

Keywords: A2A adenosine receptors; acute ischemic stroke; biophysical stimulation; neuroprotection; pulsed electromagnetic fields.

PMID: 34480781 DOI: 10.1111/ner.13489