Astroglial Alterations in the Hippocampus of Rats Submitted to a Single Trans-Cranial Direct Current Stimulation Trial.

Evidence indicates that transcranial direct current stimulation (tDCS) provides therapeutic benefits in different situations, such as epilepsy, depression, inflammatory and neuropathic pain. Despite the increasing use of tDCS, its cellular and molecular basis remains unknown. Astrocytes display a close functional and structural relationship with neurons and have been identified as mediators of neuroprotection in tDCS. Considering the importance of hippocampal glutamatergic neurotransmission in nociceptive pathways, we decided to investigate short-term changes in the hippocampal astrocytes of rats subjected to tDCS, evaluating specific cellular markers (GFAP and S100B), as well as markers of astroglial activity; glutamate uptake, glutamine synthesis by glutamine synthetase (GS) and glutathione content. Data clearly show that a single session of tDCS increases the pain threshold elicited by mechanical and thermal stimuli, as evaluated by von Frey and hot plate tests, respectively. These changes involve inflammatory and astroglial neurochemical changes in the hippocampus, based on specific changes in cell markers, such as S100B and GS. Alterations in S100B were also observed in the cerebrospinal fluid of tDCS animals and, most importantly, specific functional changes (increased glutamate uptake and increased GS activity) were detected in hippocampal astrocytes. These findings contribute to a better understanding of tDCS as a therapeutic strategy for nervous disorders and reinforce the importance of astrocytes as therapeutic targets.

Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats.

Transcranial direct current stimulation (tDCS) has demonstrated clinical benefits such as analgesia, anti-inflammatory, and neuroprotective effects. However, the mechanisms of action of a single tDCS session are poorly characterized. The present study aimed to evaluate the effects of a single tDCS session on pain sensitivity, inflammatory parameters, and astrocyte activity in naive rats. In the first experiment, sixty-day-old male Wistar rats (n = 95) were tested for mechanical pain threshold (von Frey test). Afterward, animals were submitted to a single bimodal tDCS (0.5 mA, 20 min) or sham-tDCS session. According to the group, animals were re-tested at different time intervals (30, 60, 120 min, or 24 h) after the intervention, euthanized, and the cerebral cortex collected for biochemical analysis. A second experiment (n = 16) was performed using a similar protocol to test the hypotheses that S100B levels in the cerebrospinal fluid (CSF) are altered by tDCS. Elisa assay quantified the levels of tumor necrosis factor-alfa (TNF-α), interleukin-10 (IL10), S100 calcium-binding protein B (S100B), and Glial fibrillary acidic protein (GFAP). Data were analyzed using ANOVA and independent t-test (P < 0.05). Results showed that tDCS decreased pain sensitivity (30 and 60 min), cerebral TNF-α and S100B levels (30 min). CSF S100B levels increased 30 min after intervention. There were no differences in IL10 and GFAP levels. TCDS showed analgesic, anti-inflammatory, and neuroprotective effects in naive animals. Therefore, this non-invasive and inexpensive therapy may potentially be a preemptive alternative to reduce pain, inflammation, and neurodegeneration in situations where patients will undergo medical procedures (e.g., surgery).