Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke.

Extremely low-frequency electromagnetic stimulation (ELF-EMS) was demonstrated to be significantly beneficial in rodent models of permanent stroke. The mechanism involved enhanced cerebrovascular perfusion and endothelial cell nitric oxide production. However, the possible effect on the neuroinflammatory response and its efficacy in reperfusion stroke models remains unclear. To evaluate ELF-EMS effectiveness and possible immunomodulatory response, we studied neurological outcome, behavior, neuronal survival, and glial reactivity in a rodent model of global transient stroke treated with 13.5 mT/60 Hz. Next, we studied microglial cells migration and, in organotypic hippocampal brain slices, we assessed neuronal survival and microglia reactivity. ELF-EMS improved the neurological score and behavior in the ischemia-reperfusion model. It also improved neuronal survival and decreased glia reactivity in the hippocampus, with microglia showing the first signs of treatment effect. In vitro ELF-EMS decreased (Lipopolysaccharide) LPS and ATP-induced microglia migration in both scratch and transwell assay. Additionally, in hippocampal brain slices, reduced microglial reactivity, improved neuronal survival, and modulation of inflammation-related markers was observed. Our study is the first to show that an EMF treatment has a direct impact on microglial migration. Furthermore, ELF-EMS has beneficial effects in an ischemia/reperfusion model, which indicates that this treatment has clinical potential as a new treatment against ischemic stroke.

Factores asociados al fracaso de las terapias neuroprotectoras en fase clínica en modelos animales con isquemia cerebral / Factors associated with the failure of the neuroprotector therapies in the clinical phase of animal models with cerebral ischemia

Los accidentes cerebrovasculares se han mantenido, a nivel mundial, como la tercera causa de muerte y la primera de discapacidad. Para disminuir la incidencia de casos de isquemia o hemorragia cerebral, así como sus consecuencias, se deben poseer los conocimientos sobre dichas entidades clínicas, los factores de riesgo asociados y las alternativas preventivas y terapéuticas como estrategias neuroprotectoras. Muchas de las intervenciones médicas realizadas hasta la fecha en modelos animales han resultado insatisfactorias en la fase clínica. Por ello, se realizó una revisión de las publicaciones más recientes donde se abordan los modelos experimentales para la isquemia cerebral más utilizados en las evaluaciones de las terapias neuroprotectoras, y se pudo concluir que si se analizan los protocolos empleados en la fase preclínica podrán optimizarse las investigaciones para lograr resultados más acertados en este campo.

The strokes have been considered, worldwide, as the third cause of death and the first cause of disability. To diminish the incidence of ischemia cases or cerebral hemorrhage, as well as their consequences, one should have the knowledge on this clinical entities, the associated risk factors and preventive and therapeutic alternatives as neuroprotector strategies. Many of the medical interventions carried out so far in animal models have been unsatisfactory in the clinical phase. Reason why, a review of the most recent publications was carried out, where the most used experimental models for the cerebral ischemia in the evaluations of the neuroprotector therapies are approached, and it was concluded that if protocols used in the preclinic phase are analyzed, the investigations could be optimize to achieve more relevant results in this field.

Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke.

Cerebral stroke is a leading cause of death and adult-acquired disability worldwide. To this date, treatment options are limited; hence, the search for new therapeutic approaches continues. Electromagnetic fields (EMFs) affect a wide variety of biological processes and accumulating evidence shows their potential as a treatment for ischemic stroke. Based on their characteristics, they can be divided into stationary, pulsed, and sinusoidal EMF. The aim of this review is to provide an extensive literature overview ranging from in vitro to even clinical studies within the field of ischemic stroke of all EMF types. A thorough comparison between EMF types and their effects is provided, as well as an overview of the signal pathways activated in cell types relevant for ischemic stroke such as neurons, microglia, astrocytes, and endothelial cells. We also discuss which steps have to be taken to improve their therapeutic efficacy in the frame of the clinical translation of this promising therapy.

Modelos y ensayos para el estudio de la angiogénesis / Models and trials for angiogenesis study

La angiogénesis, que conduce a la formación de redes capilares, tiene un rol importante en un elevado número de eventos fisiológicos y patológicos, entre los cuales figuran el desarrollo embrionario, la cicatrización de heridas, la artritis, el crecimiento tumoral, la metástasis y los procesos isquémicos, como uno de los mecanismos de la protección endógena y exógena. A tales efectos se analizan los métodos más utilizados actualmente tanto in vivo como in vitro para los estudios de angiogénesis; también se destacan las ventajas y desventajas de cada uno y se enfatiza en la combinación de ambos.

The angiogenesis that leads to the formation of capillary nets, has an important role in a high number of physiological and pathological events, among which we can mention the embryonic development, wounds healing, arthritis, tumoral growth, metastasis and in the ischemic processes as one of the mechanisms of the endogenous and exogenous protection. To such effects the most used methods at the moment are analyzed either in vivo or in vitro for the angiogenesis studies; advantages and disadvantages of each one are highlighted too and the combination of both is emphasized.

Modelos y ensayos para el estudio de la angiogénesis / Models and trials for angiogenesis study

La angiogénesis, que conduce a la formación de redes capilares, tiene un rol importante en un elevado número de eventos fisiológicos y patológicos, entre los cuales figuran el desarrollo embrionario, la cicatrización de heridas, la artritis, el crecimiento tumoral, la metástasis y los procesos isquémicos, como uno de los mecanismos de la protección endógena y exógena. A tales efectos se analizan los métodos más utilizados actualmente tanto in vivo como in vitro para los estudios de angiogénesis; también se destacan las ventajas y desventajas de cada uno y se enfatiza en la combinación de ambos(AU)

The angiogenesis that leads to the formation of capillary nets, has an important role in a high number of physiological and pathological events, among which we can mention the embryonic development, wounds healing, arthritis, tumoral growth, metastasis and in the ischemic processes as one of the mechanisms of the endogenous and exogenous protection. To such effects the most used methods at the moment are analyzed either in vivo or in vitro for the angiogenesis studies; advantages and disadvantages of each one are highlighted too and the combination of both is emphasized(AU)