Transcranial Direct Current Stimulation for Improvement of Neurotransplantation Outcomes in Rats with 6-Hydroxydopamine-Induced Parkinsonism

Introduction. With the number of patients with Parkinson's disease steadily growing, the need for novel treatment approaches is increasing. Combining transplantation of neuronal progenitors derived from induced pluripotent stem cells and transcranial direct current stimulation (tDCS) is among the promising methods. Aim: to examine the effect of tDCS on the cell graft condition and motor symptoms of Parkinson's syndrome in rats. Materials and methods. Parkinson's syndrome was modeled in Wistar rats by the unilateral intranigral injection of 6-hydroxydopamine (6-OHDA; 12 μg in 3 μL) The model rats underwent neurotransplantation (3 × 105 cells in 10 μL) into the caudate nuclei on the affected side. The animals underwent tDCS for 14 days. Behavioral changes were analyzed by open field and beam-walking tests. Development and morphological characteristics of the graft were assessed by the morphochemical study. Results. Neurotransplantation had no significant effect on the behavior of rats with parkinsonism; however, combined with tDCS, it increased motor activity during the open field tests compared with the group of model rats (р = 0.0014) and mitigated their anxiety-related behaviors (р = 0.048) in tests at 3 weeks after the transplantation. These effects were not observed in tests at 3 months. The morphochemical study revealed larger graft sizes in the animals that underwent tDCS compared with the controls and cell shift to the marginal zone of the graft. Stimulation was also shown to induce division of a part of cells at early stages of differentiation and promote active synaptogenesis. Conclusion. Combining neurotransplantation and tDCS in the 6-OHDA-induced model of parkinsonism demonstrated its potential to manage both motor and non-motor symptoms. Optimizing protocols of transplantation and tDCS and evaluating their long-term efficacy and safety are required to successfully implement this method into clinical practice.