L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1

Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International journal of molecular sciences 2024-01, Vol.25 (2), p.1232
Hauptverfasser: Geiseler, Samuel J., Hadzic, Alena, Lambertus, Marvin, Forbord, Karl Martin, Sajedi, Ghazal, Liesz, Arthur, Morland, Cecilie
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 2
container_start_page 1232
container_title International journal of molecular sciences
container_volume 25
creator Geiseler, Samuel J.
Hadzic, Alena
Lambertus, Marvin
Forbord, Karl Martin
Sajedi, Ghazal
Liesz, Arthur
Morland, Cecilie
description Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke by permanent occlusion of the distal medial cerebral artery of wild-type mice and knockout mice for the lactate receptor hydroxycarboxylic acid receptor 1 (HCA1). At 24 h and 48 h after stroke induction, we injected L-lactate intraperitoneal. The resulting atrophy was measured in Nissl-stained brain sections, and capillary density and neurogenesis were measured after immunolabeling and confocal imaging. In wild-type mice, L-lactate treatment resulted in an HCA1-dependent reduction in the lesion volume accompanied by enhanced angiogenesis. In HCA1 knockout mice, on the other hand, there was no increase in angiogenesis and no reduction in lesion volume in response to L-lactate treatment. Nevertheless, the lesion volumes in HCA1 knockout mice—regardless of L-lactate treatment—were smaller than in control mice, indicating a multifactorial role of HCA1 in stroke. Our findings suggest that L-lactate administered 24 h and 48 h after stroke is protective in stroke. This represents a time window where no effective treatment options are currently available.
doi_str_mv 10.3390/ijms25021232
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2919740048</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2918769361</sourcerecordid><originalsourceid>FETCH-LOGICAL-c334t-536f353bf6fff5a1f39f9d5482c5ff4baa658ea3d85494370543f130df9bbfae3</originalsourceid><addsrcrecordid>eNpd0c1Kw0AQB_AgCtbqzQdY8OLB6H4m2WMpagtBQes5bJJZmppm4-6m6AP43m6oYPE0_8Nvd4aZKLok-JYxie-azdZRgSmhjB5FE8IpjTFO0uODfBqdObfBOBAhJ9F3Hueq8soDWllQfgudR8ojytEaqa5GPBuD9mDRrBoCu__swTajUy169da8A1o69ASDNb01Hirf7ADtGhUehKh8YzpkNPJrQH_dXqCC3huLFvMZOY9OtGodXPzWafT2cL-aL-L8-XE5n-VxxRj3sWCJZoKVOtFaC0U0k1rWgme0ElrzUqlEZKBYnQkuOUux4EwThmsty1IrYNPoev9vGPRjAOeLbeMqaFvVgRlcQSWRKceYZ4Fe_aMbM9guTDeqLE0kS0hQN3tVWeOcBV30YTfKfhUEF-NNisObsB9z7H5r</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2918769361</pqid></control><display><type>article</type><title>L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Geiseler, Samuel J. ; Hadzic, Alena ; Lambertus, Marvin ; Forbord, Karl Martin ; Sajedi, Ghazal ; Liesz, Arthur ; Morland, Cecilie</creator><creatorcontrib>Geiseler, Samuel J. ; Hadzic, Alena ; Lambertus, Marvin ; Forbord, Karl Martin ; Sajedi, Ghazal ; Liesz, Arthur ; Morland, Cecilie</creatorcontrib><description>Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke by permanent occlusion of the distal medial cerebral artery of wild-type mice and knockout mice for the lactate receptor hydroxycarboxylic acid receptor 1 (HCA1). At 24 h and 48 h after stroke induction, we injected L-lactate intraperitoneal. The resulting atrophy was measured in Nissl-stained brain sections, and capillary density and neurogenesis were measured after immunolabeling and confocal imaging. In wild-type mice, L-lactate treatment resulted in an HCA1-dependent reduction in the lesion volume accompanied by enhanced angiogenesis. In HCA1 knockout mice, on the other hand, there was no increase in angiogenesis and no reduction in lesion volume in response to L-lactate treatment. Nevertheless, the lesion volumes in HCA1 knockout mice—regardless of L-lactate treatment—were smaller than in control mice, indicating a multifactorial role of HCA1 in stroke. Our findings suggest that L-lactate administered 24 h and 48 h after stroke is protective in stroke. This represents a time window where no effective treatment options are currently available.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25021232</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Angiogenesis ; Blood vessels ; Brain ; Growth factors ; Hypoxia ; Ischemia ; Neurogenesis ; Stroke</subject><ispartof>International journal of molecular sciences, 2024-01, Vol.25 (2), p.1232</ispartof><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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-c334t-536f353bf6fff5a1f39f9d5482c5ff4baa658ea3d85494370543f130df9bbfae3</citedby><cites>FETCH-LOGICAL-c334t-536f353bf6fff5a1f39f9d5482c5ff4baa658ea3d85494370543f130df9bbfae3</cites><orcidid>0000-0002-1776-1821 ; 0000-0003-1322-214X ; 0000-0002-1332-3816</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Geiseler, Samuel J.</creatorcontrib><creatorcontrib>Hadzic, Alena</creatorcontrib><creatorcontrib>Lambertus, Marvin</creatorcontrib><creatorcontrib>Forbord, Karl Martin</creatorcontrib><creatorcontrib>Sajedi, Ghazal</creatorcontrib><creatorcontrib>Liesz, Arthur</creatorcontrib><creatorcontrib>Morland, Cecilie</creatorcontrib><title>L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1</title><title>International journal of molecular sciences</title><description>Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke by permanent occlusion of the distal medial cerebral artery of wild-type mice and knockout mice for the lactate receptor hydroxycarboxylic acid receptor 1 (HCA1). At 24 h and 48 h after stroke induction, we injected L-lactate intraperitoneal. The resulting atrophy was measured in Nissl-stained brain sections, and capillary density and neurogenesis were measured after immunolabeling and confocal imaging. In wild-type mice, L-lactate treatment resulted in an HCA1-dependent reduction in the lesion volume accompanied by enhanced angiogenesis. In HCA1 knockout mice, on the other hand, there was no increase in angiogenesis and no reduction in lesion volume in response to L-lactate treatment. Nevertheless, the lesion volumes in HCA1 knockout mice—regardless of L-lactate treatment—were smaller than in control mice, indicating a multifactorial role of HCA1 in stroke. Our findings suggest that L-lactate administered 24 h and 48 h after stroke is protective in stroke. This represents a time window where no effective treatment options are currently available.</description><subject>Angiogenesis</subject><subject>Blood vessels</subject><subject>Brain</subject><subject>Growth factors</subject><subject>Hypoxia</subject><subject>Ischemia</subject><subject>Neurogenesis</subject><subject>Stroke</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpd0c1Kw0AQB_AgCtbqzQdY8OLB6H4m2WMpagtBQes5bJJZmppm4-6m6AP43m6oYPE0_8Nvd4aZKLok-JYxie-azdZRgSmhjB5FE8IpjTFO0uODfBqdObfBOBAhJ9F3Hueq8soDWllQfgudR8ojytEaqa5GPBuD9mDRrBoCu__swTajUy169da8A1o69ASDNb01Hirf7ADtGhUehKh8YzpkNPJrQH_dXqCC3huLFvMZOY9OtGodXPzWafT2cL-aL-L8-XE5n-VxxRj3sWCJZoKVOtFaC0U0k1rWgme0ElrzUqlEZKBYnQkuOUux4EwThmsty1IrYNPoev9vGPRjAOeLbeMqaFvVgRlcQSWRKceYZ4Fe_aMbM9guTDeqLE0kS0hQN3tVWeOcBV30YTfKfhUEF-NNisObsB9z7H5r</recordid><startdate>20240119</startdate><enddate>20240119</enddate><creator>Geiseler, Samuel J.</creator><creator>Hadzic, Alena</creator><creator>Lambertus, Marvin</creator><creator>Forbord, Karl Martin</creator><creator>Sajedi, Ghazal</creator><creator>Liesz, Arthur</creator><creator>Morland, Cecilie</creator><general>MDPI AG</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1776-1821</orcidid><orcidid>https://orcid.org/0000-0003-1322-214X</orcidid><orcidid>https://orcid.org/0000-0002-1332-3816</orcidid></search><sort><creationdate>20240119</creationdate><title>L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1</title><author>Geiseler, Samuel J. ; Hadzic, Alena ; Lambertus, Marvin ; Forbord, Karl Martin ; Sajedi, Ghazal ; Liesz, Arthur ; Morland, Cecilie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c334t-536f353bf6fff5a1f39f9d5482c5ff4baa658ea3d85494370543f130df9bbfae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>Blood vessels</topic><topic>Brain</topic><topic>Growth factors</topic><topic>Hypoxia</topic><topic>Ischemia</topic><topic>Neurogenesis</topic><topic>Stroke</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geiseler, Samuel J.</creatorcontrib><creatorcontrib>Hadzic, Alena</creatorcontrib><creatorcontrib>Lambertus, Marvin</creatorcontrib><creatorcontrib>Forbord, Karl Martin</creatorcontrib><creatorcontrib>Sajedi, Ghazal</creatorcontrib><creatorcontrib>Liesz, Arthur</creatorcontrib><creatorcontrib>Morland, Cecilie</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Geiseler, Samuel J.</au><au>Hadzic, Alena</au><au>Lambertus, Marvin</au><au>Forbord, Karl Martin</au><au>Sajedi, Ghazal</au><au>Liesz, Arthur</au><au>Morland, Cecilie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1</atitle><jtitle>International journal of molecular sciences</jtitle><date>2024-01-19</date><risdate>2024</risdate><volume>25</volume><issue>2</issue><spage>1232</spage><pages>1232-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Stroke is the main cause for acquired disabilities. Pharmaceutical or mechanical removal of the thrombus is the cornerstone of stroke treatment but can only be administered to a subset of patients and within a narrow time window. Novel treatment options are therefore required. Here we induced stroke by permanent occlusion of the distal medial cerebral artery of wild-type mice and knockout mice for the lactate receptor hydroxycarboxylic acid receptor 1 (HCA1). At 24 h and 48 h after stroke induction, we injected L-lactate intraperitoneal. The resulting atrophy was measured in Nissl-stained brain sections, and capillary density and neurogenesis were measured after immunolabeling and confocal imaging. In wild-type mice, L-lactate treatment resulted in an HCA1-dependent reduction in the lesion volume accompanied by enhanced angiogenesis. In HCA1 knockout mice, on the other hand, there was no increase in angiogenesis and no reduction in lesion volume in response to L-lactate treatment. Nevertheless, the lesion volumes in HCA1 knockout mice—regardless of L-lactate treatment—were smaller than in control mice, indicating a multifactorial role of HCA1 in stroke. Our findings suggest that L-lactate administered 24 h and 48 h after stroke is protective in stroke. This represents a time window where no effective treatment options are currently available.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/ijms25021232</doi><orcidid>https://orcid.org/0000-0002-1776-1821</orcidid><orcidid>https://orcid.org/0000-0003-1322-214X</orcidid><orcidid>https://orcid.org/0000-0002-1332-3816</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1422-0067
ispartof International journal of molecular sciences, 2024-01, Vol.25 (2), p.1232
issn 1422-0067
1661-6596
1422-0067
language eng
recordid cdi_proquest_miscellaneous_2919740048
source MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Angiogenesis
Blood vessels
Brain
Growth factors
Hypoxia
Ischemia
Neurogenesis
Stroke
title L-Lactate Treatment at 24 h and 48 h after Acute Experimental Stroke Is Neuroprotective via Activation of the L-Lactate Receptor HCA1
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T23%3A44%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=L-Lactate%20Treatment%20at%2024%20h%20and%2048%20h%20after%20Acute%20Experimental%20Stroke%20Is%20Neuroprotective%20via%20Activation%20of%20the%20L-Lactate%20Receptor%20HCA1&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Geiseler,%20Samuel%20J.&rft.date=2024-01-19&rft.volume=25&rft.issue=2&rft.spage=1232&rft.pages=1232-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms25021232&rft_dat=%3Cproquest_cross%3E2918769361%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2918769361&rft_id=info:pmid/&rfr_iscdi=true