{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:08:21Z","timestamp":1788966501568,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Therapeutic options for the acute phase of ischemic stroke remain limited. Transcranial direct current stimulation (tDCS) and mitochondrial transplantation have emerged as promising neuroprotective approaches, but their individual efficacy is variable. We hypothesized that combining these two therapies would produce additive benefits for post-stroke recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Focal cortical ischemia was induced in mice using photothrombotic technique. Mice were randomly assigned to receive sham treatment, tDCS, mitochondrial transplantation, or combined treatment. Grid-walking, cylinder tests and 2,3,5-triphenyltetrazolium chloride staining were used to assess motor recovery and infarct volume, respectively. Immunofluorescence staining, and western blotting were performed to determine mitochondrial internalization and polarization of astrocytes\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combining tDCS with mitochondrial transplantation resulted in a significantly greater reduction in infarct volume and improvement in locomotor function compared to either treatment alone. Interestingly, tDCS specifically enhanced the uptake of exogenous mitochondria by astrocytes. This was associated with a significant increase in beneficial A2 astrocytes and decrease in detrimental A1 astrocytes. Mechanistically, the combined treatment led to a marked upregulation of CD38 in astrocytes, suggesting their involvement in the tDCS-facilitated mitochondrial endocytosis. Suppression of CD38 expression by short interfering RNA attenuated astrocyte mitochondrial endocytosis and A2 phenotype induced by tDCS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that combining tDCS with mitochondrial transplantation conferred superior neuroprotection against ischemic brain damage than either treatment alone, and may represent a promising strategy for ischemic stroke treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1855078","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:10:54Z","timestamp":1788963054000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Additive protection of transcranial direct current stimulation and mitochondrial transplantation on ischemic stroke via inducing A2 astrocytes"],"prefix":"10.3389","volume":"19","author":[{"given":"Yaomin","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-ming","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]},{"name":"The Shaanxi Key Laboratory of Brain Function Analysis and Modulation, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]},{"name":"The Shaanxi Key Laboratory of Brain Function Analysis and Modulation, Xi\u2019an","place":["Shaanxi, China"]},{"name":"Department of Neurobiology, Medical College of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taozhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]},{"name":"The Shaanxi Key Laboratory of Brain Function Analysis and Modulation, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e598","DOI":"10.1161\/STROKEAHA.109.563627","article-title":"Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase\/Akt signaling pathway.","volume":"40","author":"Baba","year":"2009","journal-title":"Stroke"},{"key":"B2","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.brs.2016.06.004","article-title":"Safety of transcranial direct current stimulation: Evidence based update 2016.","volume":"9","author":"Bikson","year":"2016","journal-title":"Brain. 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