{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:47:48Z","timestamp":1792900068221,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heilongjiang Province Traditional Chinese Medicine Research Project","award":["ZHY2022-131"],"award-info":[{"award-number":["ZHY2022-131"]}]},{"name":"Ministry of Education of China\u2019s Young Backbone Scholar Program for the Central and Western Regions","award":["202412"],"award-info":[{"award-number":["202412"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Transcranial low-intensity pulsed ultrasound (LIPUS) is an emerging non-invasive modality with high spatial precision, substantial tissue penetrability, and favorable biosafety. Acting predominantly through mechanical rather than thermal bioeffects, LIPUS modulates mechanosensitive ion channels, intracellular calcium signaling, synaptic transmission, glial activation, neurovascular coupling, and, in selected settings, blood\u2013brain barrier permeability. These features support its growing application in neurological disorders. In this review, we summarize the mechanistic basis of transcranial LIPUS and discuss its therapeutic applications in Alzheimer\u2019s disease, Parkinson\u2019s disease, epilepsy, ischemic stroke, and major depressive disorder. Across these conditions, LIPUS has been associated with neuroprotection, enhanced synaptic plasticity, suppression of pathological neural activity, attenuation of neuroinflammation, promotion of vascular remodeling, and facilitation of targeted delivery through reversible blood\u2013brain barrier opening. We further highlight the major barriers to clinical translation, including heterogeneity of stimulation parameters, incomplete mechanistic understanding, limited comparability across studies, and insufficient large-scale clinical validation. Current evidence supports transcranial LIPUS as a promising ultrasound-based platform for neuromodulation and brain repair, while emphasizing the need for standardized protocols and rigorous translational studies.<\/jats:p>","DOI":"10.3389\/fneur.2026.1850924","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:22:01Z","timestamp":1784002921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcranial low-intensity pulsed ultrasound in neurological disorders: mechanisms, therapeutic applications, and translational challenges"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongbo","family":"Cai","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Che","sequence":"additional","affiliation":[{"name":"Institute of Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Hou","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]},{"name":"Institute of Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University","place":["Xi\u2019an, China"]},{"name":"College of Basic Medical and Sciences, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.clinph.2021.12.010","article-title":"Non-invasive transcranial ultrasound stimulation for neuromodulation","volume":"135","author":"Darmani","year":"2022","journal-title":"Clin Neurophysiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41467-022-28040-1","article-title":"Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification","volume":"13","author":"Yoo","year":"2022","journal-title":"Nat Commun"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation 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