Multi-Session Transcranial Direct Current Stimulation (tDCS) Elicits Inflammatory and Regenerative Processes in the Rat Brain

Abstract

Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16) were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min). Bromodeoxyuridine (BrdU) was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC). Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model

“…Some of migrated cells have expressed the neural phenotype [16, 17]. Similarly, in the transcranial direct current stimulation (tDCS), cathodal stimulation induces the recruitment of proliferating neural stem cells [32]. For migration of transplanted cells, Keuters reported that tDCS promotes the mobility of cells [33].…”

Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells

“…Understanding how endogenous EFs could guide cell migration and how an applied EF could potentially be leveraged to modulate this process provide a rationale for new therapeutics. For example, transcranial direct current stimulation (tDCS) has shown clinical benefits for central nervous system diseases (Fregni et al, 2015) and was able to promote cathodal accumulation of endogenous neural stem cells (Rueger et al, 2012). As more is learned about the role of bioelectricity on cell function it is likely that new opportunities for interventions will emerge.…”

Depression as a Microglial Disease

“…Furthermore, ECS treatment counteracted the suppressive effect of chronic corticosterone administration on microglial proliferation [156]. A different type of brain stimulation (repeated transcranial direct current stimulation) was also found to increase the number and activation status of cortical microglia [160].…”