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Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)
The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance...
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| Published in: | Scientific reports 2020-10, Vol.10 (1), p.18488-18488, Article 18488 |
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| description | The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (D
eff
) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, D
eff
increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in D
eff
returned to the control level 25–30 min post tDCS. A mathematical model for D
eff
in the extracelluar space (ECS) further predicts that this dose of tDCS increases D
eff
by transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies. |
| doi_str_mv | 10.1038/s41598-020-75460-4 |
| format | article |
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eff
) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, D
eff
increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in D
eff
returned to the control level 25–30 min post tDCS. A mathematical model for D
eff
in the extracelluar space (ECS) further predicts that this dose of tDCS increases D
eff
by transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-75460-4</identifier><identifier>PMID: 33116214</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/378 ; 631/443 ; 631/57 ; 639/166 ; Animal tissues ; Animals ; Brain ; Brain - drug effects ; Brain - physiology ; Carotid Arteries ; Carotid artery ; Diffusion ; Diffusion coefficient ; Electrical stimulation of the brain ; Endothelial cells ; Endothelial Cells - metabolism ; ESB ; Evoked Potentials, Motor ; Excitability ; Extracellular matrix ; Extracellular Matrix - metabolism ; Female ; Fluorescein ; Humanities and Social Sciences ; Hydraulics ; Mathematical models ; Metabolism ; Microscopy ; Microscopy, Fluorescence ; Models, Theoretical ; Motor Cortex - physiology ; multidisciplinary ; Neuronal Plasticity ; Neuronal-glial interactions ; Neuroplasticity ; Permeability ; Rats ; Rats, Sprague-Dawley ; Science ; Science (multidisciplinary) ; Sodium ; Solutes ; Solvents ; Synaptic plasticity ; Transcranial Direct Current Stimulation ; Veins & arteries</subject><ispartof>Scientific reports, 2020-10, Vol.10 (1), p.18488-18488, Article 18488</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-bd6b9c35374eb465a2bb6b7ea78a987564c451d60a6eb993b3f94d5cc1f162c03</citedby><cites>FETCH-LOGICAL-c474t-bd6b9c35374eb465a2bb6b7ea78a987564c451d60a6eb993b3f94d5cc1f162c03</cites><orcidid>0000-0001-9343-5895</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2471534301/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2471534301?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33116214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xia, Yifan</creatorcontrib><creatorcontrib>Khalid, Wasem</creatorcontrib><creatorcontrib>Yin, Zhaokai</creatorcontrib><creatorcontrib>Huang, Guangyao</creatorcontrib><creatorcontrib>Bikson, Marom</creatorcontrib><creatorcontrib>Fu, Bingmei M.</creatorcontrib><title>Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (D
eff
) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, D
eff
increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in D
eff
returned to the control level 25–30 min post tDCS. A mathematical model for D
eff
in the extracelluar space (ECS) further predicts that this dose of tDCS increases D
eff
by transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies.</description><subject>631/378</subject><subject>631/443</subject><subject>631/57</subject><subject>639/166</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - physiology</subject><subject>Carotid Arteries</subject><subject>Carotid artery</subject><subject>Diffusion</subject><subject>Diffusion coefficient</subject><subject>Electrical stimulation of the brain</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>ESB</subject><subject>Evoked Potentials, Motor</subject><subject>Excitability</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>Fluorescein</subject><subject>Humanities and Social Sciences</subject><subject>Hydraulics</subject><subject>Mathematical models</subject><subject>Metabolism</subject><subject>Microscopy</subject><subject>Microscopy, Fluorescence</subject><subject>Models, Theoretical</subject><subject>Motor Cortex - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xia, Yifan</au><au>Khalid, Wasem</au><au>Yin, Zhaokai</au><au>Huang, Guangyao</au><au>Bikson, Marom</au><au>Fu, Bingmei M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-10-28</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>18488</spage><epage>18488</epage><pages>18488-18488</pages><artnum>18488</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (D
eff
) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, D
eff
increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in D
eff
returned to the control level 25–30 min post tDCS. A mathematical model for D
eff
in the extracelluar space (ECS) further predicts that this dose of tDCS increases D
eff
by transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33116214</pmid><doi>10.1038/s41598-020-75460-4</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-9343-5895</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/378 631/443 631/57 639/166 Animal tissues Animals Brain Brain - drug effects Brain - physiology Carotid Arteries Carotid artery Diffusion Diffusion coefficient Electrical stimulation of the brain Endothelial cells Endothelial Cells - metabolism ESB Evoked Potentials, Motor Excitability Extracellular matrix Extracellular Matrix - metabolism Female Fluorescein Humanities and Social Sciences Hydraulics Mathematical models Metabolism Microscopy Microscopy, Fluorescence Models, Theoretical Motor Cortex - physiology multidisciplinary Neuronal Plasticity Neuronal-glial interactions Neuroplasticity Permeability Rats Rats, Sprague-Dawley Science Science (multidisciplinary) Sodium Solutes Solvents Synaptic plasticity Transcranial Direct Current Stimulation Veins & arteries |
| title | Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS) |
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