tDCS Accelerates the Rehabilitation of MCAO-Induced Motor Function Deficits via Neurogenesis Modulated by the Notch1 Signaling Pathway

Abstract

Background. Ischemic stroke carries a high mortality rate and is a leading cause of severe neurological disability. However, the efficacy of current therapeutic options remains limited. Objective. We aimed to investigate the treatment efficacy of transcranial direct current stimulation (tDCS) in motor function rehabilitation after ischemic stroke and explore the underlying mechanisms. Methods. Male Sprague-Dawley rats with epicranial electrodes were used to establish pathogenetic model through temporary right middle cerebral artery occlusion (MCAO). Subsequently, animals were randomly divided into 4 groups: MCAO + tDCS/sham tDCS, Control + tDCS/sham tDCS. Animals in the groups with tDCS underwent 10 days of cathodal tDCS totally (500 µA, 15 minutes, once a day). During and after tDCS treatment, the motor functions of the animals, ischemic damage area, proliferation and differentiation of neural stem cells (NSCs), and distribution, and protein expression of Notch1 signaling molecules were detected. Results. The rehabilitation of MCAO-induced motor function deficits was dramatically accelerated by tDCS treatment. NSC proliferation in the subventricular zone (SVZ) was significantly increased after MCAO surgery, and tDCS treatment promoted this process. Additionally, NSCs probably migrated from the SVZ to the ischemic striatum and then differentiated into neurons and oligodendrocytes after MCAO surgery, both of which processes were accelerated by tDCS treatment. Finally, tDCS treatment inhibited the activation of Notch1 signaling in NSCs in the ischemic striatum, which may be involved in NSC differentiation in the MCAO model. Conclusion. Our results suggest that tDCS may exert therapeutic efficacy after ischemic stroke in a regenerative medical perspective.