Repetitive transcranial magnetic stimulation (rTMS) for multiple neurological conditions in rodent animal models: A systematic review

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique. Recently, rTMS has shown promising therapeutic potential in multiple neurological conditions. Nevertheless, challenges remain in the clinical application of rTMS, which mainly due to the lack of consensus on optimal stimulation protocols and poor understanding of the exact targets driving its action. Experimental animal research with more controllable factors may contribute to fill our knowledge gap in this area, and to accelerate the development of clinical translation studies. Therefore, the current study was designed to systematically review the effects of rTMS on animal models of certain diseases and evaluate its potential mechanisms of action, which may guide future studies aiming to improve the therapeutic utilization for these diseases.Methods: A systematic literature search was conducted through the PubMed online database on August 19, 2021. The search strategy consisted of two main components: rTMS and stroke, Alzheimer's disease (AD), vascular dementia (VaD), and Parkinson's disease (PD), with results limited to animal studies.Results: We identified 41 animal studies, 21 that examined stroke, 8 that investigated Alzheimer's disease, 5 that studied vascular dementia, and 7 that examined Parkinson's disease, all of these studies were conducted in rodents (rat and mice). Despite variations in study design and research methods, the therapeutic benefits of rTMS, as reflected in the alleviation of disease-related symptoms and pathological improvements, have been reported in these studies. rTMS induces multi-directional changes at the cellular and molecular levels, including a significant contribution to synaptic plasticity. Furthermore, the curative effects of rTMS are related to stimulation parameters, with high-frequency rTMS reported has better therapeutic efficacy in several studies. In terms of safety, one study involving combination therapy reported the adverse effects of rTMS administration.Conclusions: rTMS have shown encouraging therapeutic value in rodent models of stroke, AD, VaD, and PD. Nonetheless, the optimal protocols and exact target of action for this therapy remain to be determined. Correspondingly, further research is still needed to bridge the translation gap between rodent experiments and clinical application, which might lead to new directions in the treatment of multiple neurological disorders.