REVIEW article
Front. Neurosci.
Sec. Translational Neuroscience
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1667100
This article is part of the Research TopicNeuromodulation Techniques, Mechanisms, and Potential Benefits for Physical Activity Participation and Human PerformanceView all 10 articles
Understanding the Effects of Transcranial Direct Current Stimulation on the Neurovascular Unit: A Narrative Review
Provisionally accepted
- 1University of Canberra Department of Psychology, Canberra, Australia
- 2Universitat der Bundeswehr Munchen Institut fur Sportwissenschaft, Neubiberg, Germany
- 3University of Canberra Faculty of Health, Canberra, Australia
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Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has demonstrated promise both for treating diverse clinical conditions and for enhancing brain function in healthy adults. Despite increasing popularity, the precise physiological mechanisms underlying its effects remain poorly defined, contributing to inconsistent findings. This review synthesises current evidence for both acute and enduring effects of tDCS across the complete neurovascular unit, encompassing neurons, astrocytes, oligodendrocytes, microglia, the blood-brain barrier, metabolic pathways, and immune responses. We review recent transcriptomic, proteomic, and metabolomic studies which reveal that tDCS induces coordinated molecular changes, including modulation of genes involved in inflammation, neurogenesis, calcium signalling, mitochondrial metabolism, and synaptic plasticity proteins. We emphasise significant gaps in current literature, particularly the limited consideration given to astrocytes and oligodendrocytes, despite their known importance in activity-dependent plasticity. We conclude that the neurovascular unit represents an integrative and complex target of tDCS, suggesting that comprehensive modulation of these components may better explain observed changes in cognitive, behavioural, and neuropsychological outcomes. Future research should move beyond a neuron-centric perspective, embracing a more integrative framework that considers interactions among all elements of the neurovascular unit. Such a holistic approach will enhance our understanding of how tDCS exerts its effects, thereby improving its clinical utility.
Keywords: tDCS, mechanisms, Neuromodulation, review, neurovascular unit
Received: 16 Jul 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Lewis, Rattray and Flood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Aidan Lewis, aidan.lewis@canberra.edu.au
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