Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice

Abstract

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury.

Trans-Spinal Direct Current Stimulation in Spasticity: A Literature Mini-Review

“…Hence, a given electrical field polarity can increase spinal tract excitability in the white matter and simultaneously decrease excitability in neural elements in the gray matter, or vice versa. There is some pioneering work exploring the effects of tsDCS in animals (Fuortes, 1954), showing the potential of this technique in modulating spinal circuitry (Ahmed, 2011(Ahmed, , 2013(Ahmed, , 2014b(Ahmed, , 2016Ahmed and Wieraszko, 2012;Samaddar et al, 2017).…”

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes

“…Finally, a novel and exciting mechanism of action has been recently proposed by Samaddar and co-workers [353]: they found that tsDCS also modulates the migration and proliferation of adult newly born spinal cells in mice, a cell population implicated in learning and memory; although the mechanisms are not fully understood, these findings suggest that tsDCS could be used, also in humans, as an early treatment to improve motor recovery in spinal cord lesions. In this connection, another study has confirmed that tsDCS increases locomotor skill acquisition and retention in healthy volunteers [354].…”

Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

“…It has been proposed that tsDCS can cause long‐term changes in the excitability of spinal cord circuits (Bolzoni & Jankowska, ; Samaddar et al . ; Song et al . ; Wieraszko & Ahmed, ; Ahmed, , ).…”