Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models

Abstract

Background. Stroke is the leading cause of adult disability, but treatment options remain limited, leaving most patients with incomplete recovery. Patient and animal studies have shown potential of noninvasive brain stimulation (NIBS) strategies to improve function after stroke. However, mechanisms underlying therapeutic effects of NIBS are unclear and there is no consensus on which NIBS protocols are most effective. Objective. Provide a review of articles that assessed effects and mechanisms of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in animal stroke models. Methods. Articles were searched in PubMed, including cross-references. Results. Nineteen eligible studies reporting effects of rTMS or tDCS after stroke in small rodents were identified. Seventeen of those described improved functional recovery or neuroprotection compared with untreated control or sham-stimulated groups. The effects of rTMS could be related to molecular mechanisms associated with ischemic tolerance, neuroprotection, anti-apoptosis, neurogenesis, angiogenesis, or neuroplasticity. Favorable outcome appeared most effectively when using high-frequency (>5 Hz) rTMS or intermittent theta burst stimulation of the ipsilesional hemisphere. tDCS effects were strongly dependent on stimulation polarity and onset time. Although these findings are promising, most studies did not meet Good Laboratory Practice assessment criteria. Conclusions. Despite limited data availability, animal stroke model studies demonstrate potential of NIBS to promote stroke recovery through different working mechanisms. Future studies in animal stroke models should adhere to Good Laboratory Practice guidelines and aim to further develop clinically applicable treatment protocols by identifying most favorable stimulation parameters, treatment onset, adjuvant therapies, and underlying modes of action.

Discussion on the Rehabilitation of Stroke Hemiplegia Based on Interdisciplinary Combination of Medicine and Engineering

“…Cathodic (−) tDCS has also been shown to reduce edema, inflammation, cell apoptosis, and cortical glutamate, creatine, and taurine levels. Cathodic (−) tDCS also preserves cell structure within the cerebral cortex which can lead to reduction in infarct volume and better recovery of function [ 64 ]. Other theories of cerebral interactions during the recovery from exercise suggest that the cerebral hemispheres work in cooperation rather than competition.…”

Trends of Repetitive Transcranial Magnetic Stimulation From 2009 to 2018: A Bibliometric Analysis

“…III. Recovery: rTMS has a positive impact on functional recovery, such as limb motor recovery in stroke patients; however, optimal rTMS parameters and high-quality evidence require further research (Pollock et al, 2014;Boonzaier et al, 2018;Yang et al, 2018;Xiang et al, 2019). IV.…”

“…rTMS is the most widely used non-invasive brain stimulation technique currently available (George and Aston-Jones, 2010;Miniussi et al, 2013;Cirillo et al, 2017;Lowe et al, 2017;Lucena et al, 2019). Numerous studies have investigated the effects and mechanisms underlying various rTMS protocols, which remain incompletely understood (Fitzgerald et al, 2006b;Boonzaier et al, 2018;Zorzo et al, 2019). Low-frequency (≤1.0 Hz) rTMS usually reduces cortical excitability, whereas high-frequency (>1.0 Hz) rTMS (HF-rTMS) raises excitability (Maeda et al, 2000;Rossini et al, 2015).…”

Regenerative Rehabilitation for Stroke Recovery by Inducing Synergistic Effects of Cell Therapy and Neurorehabilitation on Motor Function: A Narrative Review of Pre-Clinical Studies

“…Many studies have focused on epidural cortical stimulation (CS), in which electrodes are neurosurgically placed on the surface of the brain for stimulation; and noninvasive brain stimulation (NIBS) techniques, which included transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). Recent years have seen enthusiastic research activity on stroke treatment using brain stimulation in both humans and laboratory animals with promising results [46][47][48]. Animal experiments are slowly revealing the effects of brain stimulation at the cellular level (Figure 1), and studies have reported the effects of combining these techniques with cell therapy.…”