Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

Abstract

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in the Presence of Endogenous Electric Fields in Mouse Brains

“…The lineage and differentiation state of cells can also modify their response to EFs (Patel and Poo, 1982;Babona-Pilipos et al, 2011;Baer et al, 2015;Li et al, 2015). With respect to NPCs, we have shown that undifferentiated NPCs migrate in the presence of EFs but not their differentiated progeny (Babona-Pilipos et al, 2011).…”

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

“…Rat cortical astrocytes migrate anodally and show increased proliferation in an EF of 40 mV/mm (Baer et al, 2015). Nerves and Schwann cells have a galvanotaxis threshold of ca.…”

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes

“…Unlike other studies of electrical stimulation on cultured astrocytes that mostly focused on the applied current amplitude (4 -1500 mV/mm) rather than the frequency (74)(75)(76)(77)(78), this report, to the best of our knowledge, demonstrates for the first time that the mobility of intracellular vesicles in astrocytes can be increased only at a low-frequency electrical stimulation. This frequency-dependent effect of electrical fields on cellular functionalities likely applies to other cell types, such as neurons, microglial, or even cancer cells.…”