Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke
Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles...
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| creator | Schleicher, Nadine Tomkins, Amelia J Kampschulte, Marian Hyvelin, Jean-Marc Botteron, Catherine Juenemann, Martin Yeniguen, Mesut Krombach, Gabriele A Kaps, Manfred Spratt, Neil J Gerriets, Tibo Nedelmann, Max |
| description | Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.
We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.
Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p0.1).
Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory. |
| doi_str_mv | 10.1371/journal.pone.0152898 |
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We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.
Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1).
Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0152898</identifier><identifier>PMID: 27077372</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Blood clots ; Blood vessels ; Brain research ; Care and treatment ; Cerebral blood flow ; Clinical outcomes ; Computed tomography ; Disease Models, Animal ; Formulations ; Genetically modified mice ; Heart ; Ischemia ; Lasers ; Male ; Medical research ; Medicine and Health Sciences ; Microbubbles ; Microbubbles - therapeutic use ; Microvasculature ; Nanotechnology ; Neurology ; Occlusion ; Patient outcomes ; Pharmacy ; Rats ; Rats, Wistar ; Research and Analysis Methods ; Stroke ; Stroke - diagnostic imaging ; Stroke - therapy ; Studies ; Surgery ; Systematic review ; Territory ; Thrombolytic Therapy - methods ; Tomography ; Transcranial Doppler ultrasonography ; Ultrasonic Waves ; Ultrasonography ; Ultrasound ; Veins & arteries ; X-Ray Microtomography</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0152898-e0152898</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Schleicher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Schleicher et al 2016 Schleicher et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-97e49b74b87a3d9529c916058dda6d2752c0a23d0b8f27a2e5fec574c0a4ddae3</citedby><cites>FETCH-LOGICAL-c692t-97e49b74b87a3d9529c916058dda6d2752c0a23d0b8f27a2e5fec574c0a4ddae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831751/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831751/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27077372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhao, Heng</contributor><creatorcontrib>Schleicher, Nadine</creatorcontrib><creatorcontrib>Tomkins, Amelia J</creatorcontrib><creatorcontrib>Kampschulte, Marian</creatorcontrib><creatorcontrib>Hyvelin, Jean-Marc</creatorcontrib><creatorcontrib>Botteron, Catherine</creatorcontrib><creatorcontrib>Juenemann, Martin</creatorcontrib><creatorcontrib>Yeniguen, Mesut</creatorcontrib><creatorcontrib>Krombach, Gabriele A</creatorcontrib><creatorcontrib>Kaps, Manfred</creatorcontrib><creatorcontrib>Spratt, Neil J</creatorcontrib><creatorcontrib>Gerriets, Tibo</creatorcontrib><creatorcontrib>Nedelmann, Max</creatorcontrib><title>Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.
We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.
Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1).
Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.</description><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Blood clots</subject><subject>Blood vessels</subject><subject>Brain research</subject><subject>Care and treatment</subject><subject>Cerebral blood flow</subject><subject>Clinical outcomes</subject><subject>Computed tomography</subject><subject>Disease Models, Animal</subject><subject>Formulations</subject><subject>Genetically modified mice</subject><subject>Heart</subject><subject>Ischemia</subject><subject>Lasers</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Microbubbles</subject><subject>Microbubbles - therapeutic use</subject><subject>Microvasculature</subject><subject>Nanotechnology</subject><subject>Neurology</subject><subject>Occlusion</subject><subject>Patient outcomes</subject><subject>Pharmacy</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Research and Analysis Methods</subject><subject>Stroke</subject><subject>Stroke - diagnostic imaging</subject><subject>Stroke - therapy</subject><subject>Studies</subject><subject>Surgery</subject><subject>Systematic review</subject><subject>Territory</subject><subject>Thrombolytic Therapy - methods</subject><subject>Tomography</subject><subject>Transcranial Doppler ultrasonography</subject><subject>Ultrasonic Waves</subject><subject>Ultrasonography</subject><subject>Ultrasound</subject><subject>Veins & arteries</subject><subject>X-Ray Microtomography</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCIhITgocU_Y-cFaUz8qLRpqAVeLcdxWhcnLrZT6H-Pu2ZTg_aA_GDr_Lnv-c53WfYcginEDL5bu9530k43rtNTACniJX-QncISo0mBAH54dD7JnoSwBoBiXhSPsxPEAGOYodNMLFzn4sq7tnJ2F0zIf5u4yj_MMc-vjPKu6qvK6pDP2o1323S4sW5lUL2VPv8qo-7ULjddLvO5jPmVq7XNXZMvonc_9dPsUSNt0M-G_Sz7_unjt4svk8vrz7OL88uJKkoUJyXTpKwYqTiTuC4pKlUJC0B5XcuiRowiBSTCNah4g5hEmjZaUUaSlSRE47Ps5UF3Y10QQ22CgIxDSApCQCJmB6J2ci023rTS74STRtwYnF8K6aNRVgsNKlLJhiqYQjRYc9QgSmtAGAINBFXSej9E66tW10p30Us7Eh3fdGYllm4rCMeQUZgE3gwC3v3qdYiiNUFpa2WnXX94d_osVJQJffUPen92A7WUKQHTNS7FVXtRcU4oJoQnOFHTe6i0at0alRqpMck-cng7ckhM1H_iUvYhiNli_v_s9Y8x-_qIXWlp4yo420fjujAGyQFMTReC181dkSEQ-zm4rYbYz4EY5iC5vTj-oDun28bHfwFlwQKM</recordid><startdate>20160414</startdate><enddate>20160414</enddate><creator>Schleicher, Nadine</creator><creator>Tomkins, Amelia J</creator><creator>Kampschulte, Marian</creator><creator>Hyvelin, Jean-Marc</creator><creator>Botteron, Catherine</creator><creator>Juenemann, Martin</creator><creator>Yeniguen, Mesut</creator><creator>Krombach, Gabriele A</creator><creator>Kaps, Manfred</creator><creator>Spratt, Neil J</creator><creator>Gerriets, Tibo</creator><creator>Nedelmann, Max</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160414</creationdate><title>Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke</title><author>Schleicher, Nadine ; Tomkins, Amelia J ; Kampschulte, Marian ; Hyvelin, Jean-Marc ; Botteron, Catherine ; Juenemann, Martin ; Yeniguen, Mesut ; Krombach, Gabriele A ; Kaps, Manfred ; Spratt, Neil J ; Gerriets, Tibo ; Nedelmann, Max</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-97e49b74b87a3d9529c916058dda6d2752c0a23d0b8f27a2e5fec574c0a4ddae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Blood clots</topic><topic>Blood vessels</topic><topic>Brain research</topic><topic>Care and treatment</topic><topic>Cerebral blood flow</topic><topic>Clinical outcomes</topic><topic>Computed tomography</topic><topic>Disease Models, Animal</topic><topic>Formulations</topic><topic>Genetically modified mice</topic><topic>Heart</topic><topic>Ischemia</topic><topic>Lasers</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Microbubbles</topic><topic>Microbubbles - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schleicher, Nadine</au><au>Tomkins, Amelia J</au><au>Kampschulte, Marian</au><au>Hyvelin, Jean-Marc</au><au>Botteron, Catherine</au><au>Juenemann, Martin</au><au>Yeniguen, Mesut</au><au>Krombach, Gabriele A</au><au>Kaps, Manfred</au><au>Spratt, Neil J</au><au>Gerriets, Tibo</au><au>Nedelmann, Max</au><au>Zhao, Heng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-14</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0152898</spage><epage>e0152898</epage><pages>e0152898-e0152898</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.
We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.
Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1).
Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27077372</pmid><doi>10.1371/journal.pone.0152898</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-04, Vol.11 (4), p.e0152898-e0152898 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1781146440 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Biology and Life Sciences Blood clots Blood vessels Brain research Care and treatment Cerebral blood flow Clinical outcomes Computed tomography Disease Models, Animal Formulations Genetically modified mice Heart Ischemia Lasers Male Medical research Medicine and Health Sciences Microbubbles Microbubbles - therapeutic use Microvasculature Nanotechnology Neurology Occlusion Patient outcomes Pharmacy Rats Rats, Wistar Research and Analysis Methods Stroke Stroke - diagnostic imaging Stroke - therapy Studies Surgery Systematic review Territory Thrombolytic Therapy - methods Tomography Transcranial Doppler ultrasonography Ultrasonic Waves Ultrasonography Ultrasound Veins & arteries X-Ray Microtomography |
| title | Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-30T09%3A07%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sonothrombolysis%20with%20BR38%20Microbubbles%20Improves%20Microvascular%20Patency%20in%20a%20Rat%20Model%20of%20Stroke&rft.jtitle=PloS%20one&rft.au=Schleicher,%20Nadine&rft.date=2016-04-14&rft.volume=11&rft.issue=4&rft.spage=e0152898&rft.epage=e0152898&rft.pages=e0152898-e0152898&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0152898&rft_dat=%3Cgale_plos_%3EA453448178%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781146440&rft_id=info:pmid/27077372&rft_galeid=A453448178&rft_doaj_id=oai_doaj_org_article_e0b4baf5c1574f3e82f255d04720f10b&rfr_iscdi=true |