Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries
The blood–brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB. We investigated the spatial distrib...
Gespeichert in:
| Veröffentlicht in: | British journal of pharmacology 2003-12, Vol.140 (7), p.1201-1210 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1210 |
|---|---|
| container_issue | 7 |
| container_start_page | 1201 |
| container_title | British journal of pharmacology |
| container_volume | 140 |
| creator | Erdlenbruch, Bernhard Alipour, Mehrnaz Fricker, Gert Miller, David S Kugler, Wilfried Eibl, Hansjörg Lakomek, Max |
| description | The blood–brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB.
We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine‐rhodamine B200 (RB 200)–albumin in the brain of normal and C6 glioma‐bearing rats after intracarotid co‐administration of 1‐O‐pentylglycerol (200 mM). To elucidate the mechanisms involved in the alkylglycerol‐mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC)–dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1‐O‐pentylglycerol‐induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice.
Microscopic evaluation showed a marked 1‐O‐pentylglycerol‐induced extravasation of fluorescein and RB 200–albumin in the ipsilateral normal brain. In glioma‐bearing rats, increased tissue fluorescence was found in both tumor tissue and brain surrounding tumor. Confocal microscopy revealed a time‐ and concentration‐dependent accumulation of FITC–dextran 40,000 within the lumina of isolated rat brain capillaries during incubation with 1‐O‐pentylglycerol and 2‐O‐hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions. Intracarotid co‐administration of MTX and 1‐O‐pentylglycerol (200 mM) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1‐O‐pentylglycerol (P |
| doi_str_mv | 10.1038/sj.bjp.0705554 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1574140</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71423149</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4877-1af8dad4eec988a637c7aa0f426fa6c0384fa5b20f3c75c72bfcfab5fe19e1a43</originalsourceid><addsrcrecordid>eNqFkc9u1DAQxiMEokvhyhFZSHDbxU7sOLkglRVQpEpwgLM1ccapUycOdrZob30EJF6BJ-uT4P0jClw4WfL85pv55suyp4yuGC2qV7FfNf20opIKIfi9bMG4LJeiqNj9bEEplUvGquokexRjT2kqSvEwO2Fc1FLU9SL7eeautq5zW43BO-InHO3YEW_IfImkcd63tzc_mgB2JA2EYDGQ2ZM4gHMExpY4CB0S4zY-YNQ4aiQDhCsMkaSW0YdE7sF1STpn_QC3N98bhLAbE2CO-6KN3sGM7e6HHKZpmKxL6hbj4-yBARfxyfE9zb68e_t5fb68-Pj-w_rsYql5JZNTMFULLUfUdVVBWUgtAajheWmg1Olc3IBocmoKLYWWeWO0gUYYZDUy4MVp9vqgO22aAdvkZg7g1BRssrRVHqz6uzLaS9X5a8WE5IzTJPDyKBD81w3GWQ02HSXZGNFvopKM5wXjdQKf_wP2fhPGZE7lTLKaMbpTWx0gHXyMAc3vTRhVu_RV7FVKXx3TTw3P_tz_Dj_GnYAXRwCiBmcCjNrGO04UkvL95OLAfbMOt_8Zq958OueCyuIXyrjQHg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>217191100</pqid></control><display><type>article</type><title>Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Erdlenbruch, Bernhard ; Alipour, Mehrnaz ; Fricker, Gert ; Miller, David S ; Kugler, Wilfried ; Eibl, Hansjörg ; Lakomek, Max</creator><creatorcontrib>Erdlenbruch, Bernhard ; Alipour, Mehrnaz ; Fricker, Gert ; Miller, David S ; Kugler, Wilfried ; Eibl, Hansjörg ; Lakomek, Max</creatorcontrib><description>The blood–brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB.
We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine‐rhodamine B200 (RB 200)–albumin in the brain of normal and C6 glioma‐bearing rats after intracarotid co‐administration of 1‐O‐pentylglycerol (200 mM). To elucidate the mechanisms involved in the alkylglycerol‐mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC)–dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1‐O‐pentylglycerol‐induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice.
Microscopic evaluation showed a marked 1‐O‐pentylglycerol‐induced extravasation of fluorescein and RB 200–albumin in the ipsilateral normal brain. In glioma‐bearing rats, increased tissue fluorescence was found in both tumor tissue and brain surrounding tumor. Confocal microscopy revealed a time‐ and concentration‐dependent accumulation of FITC–dextran 40,000 within the lumina of isolated rat brain capillaries during incubation with 1‐O‐pentylglycerol and 2‐O‐hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions. Intracarotid co‐administration of MTX and 1‐O‐pentylglycerol (200 mM) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1‐O‐pentylglycerol (P<0.005).
In conclusion, 1‐O‐pentylglycerol increases delivery of small and large compounds to normal brain and brain tumors and this effect is mediated at least in part by enhanced permeability of tight junctions.
British Journal of Pharmacology (2003) 140, 1201–1210. doi:10.1038/sj.bjp.0705554</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0705554</identifier><identifier>PMID: 14597599</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alkylglycerol ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacokinetics ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Blood-Brain Barrier - drug effects ; blood–brain barrier ; Brain - drug effects ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; brain tumor ; Capillaries ; confocal microscopy ; drug delivery ; Fluorescein ; fluorescence markers ; Fluorescent Dyes ; Glioma - metabolism ; Glioma - pathology ; Glycerol - administration & dosage ; Glycerol - analogs & derivatives ; Glycerol - pharmacology ; Injections, Intra-Arterial ; Injections, Intraventricular ; Male ; Medical sciences ; methotrexate ; Methotrexate - administration & dosage ; Methotrexate - pharmacokinetics ; Mice ; Mice, Nude ; Microscopy, Confocal ; Neoplasm Transplantation ; Pharmacology. Drug treatments ; rat brain capillaries ; Rats ; Rats, Wistar ; tight junction ; Tissue Distribution</subject><ispartof>British journal of pharmacology, 2003-12, Vol.140 (7), p.1201-1210</ispartof><rights>2003 British Pharmacological Society</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2003</rights><rights>Copyright 2003, Nature Publishing Group 2003 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4877-1af8dad4eec988a637c7aa0f426fa6c0384fa5b20f3c75c72bfcfab5fe19e1a43</citedby><cites>FETCH-LOGICAL-c4877-1af8dad4eec988a637c7aa0f426fa6c0384fa5b20f3c75c72bfcfab5fe19e1a43</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/PMC1574140/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574140/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15370400$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14597599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Erdlenbruch, Bernhard</creatorcontrib><creatorcontrib>Alipour, Mehrnaz</creatorcontrib><creatorcontrib>Fricker, Gert</creatorcontrib><creatorcontrib>Miller, David S</creatorcontrib><creatorcontrib>Kugler, Wilfried</creatorcontrib><creatorcontrib>Eibl, Hansjörg</creatorcontrib><creatorcontrib>Lakomek, Max</creatorcontrib><title>Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The blood–brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB.
We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine‐rhodamine B200 (RB 200)–albumin in the brain of normal and C6 glioma‐bearing rats after intracarotid co‐administration of 1‐O‐pentylglycerol (200 mM). To elucidate the mechanisms involved in the alkylglycerol‐mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC)–dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1‐O‐pentylglycerol‐induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice.
Microscopic evaluation showed a marked 1‐O‐pentylglycerol‐induced extravasation of fluorescein and RB 200–albumin in the ipsilateral normal brain. In glioma‐bearing rats, increased tissue fluorescence was found in both tumor tissue and brain surrounding tumor. Confocal microscopy revealed a time‐ and concentration‐dependent accumulation of FITC–dextran 40,000 within the lumina of isolated rat brain capillaries during incubation with 1‐O‐pentylglycerol and 2‐O‐hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions. Intracarotid co‐administration of MTX and 1‐O‐pentylglycerol (200 mM) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1‐O‐pentylglycerol (P<0.005).
In conclusion, 1‐O‐pentylglycerol increases delivery of small and large compounds to normal brain and brain tumors and this effect is mediated at least in part by enhanced permeability of tight junctions.
British Journal of Pharmacology (2003) 140, 1201–1210. doi:10.1038/sj.bjp.0705554</description><subject>Alkylglycerol</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>blood–brain barrier</subject><subject>Brain - drug effects</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>brain tumor</subject><subject>Capillaries</subject><subject>confocal microscopy</subject><subject>drug delivery</subject><subject>Fluorescein</subject><subject>fluorescence markers</subject><subject>Fluorescent Dyes</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Glycerol - administration & dosage</subject><subject>Glycerol - analogs & derivatives</subject><subject>Glycerol - pharmacology</subject><subject>Injections, Intra-Arterial</subject><subject>Injections, Intraventricular</subject><subject>Male</subject><subject>Medical sciences</subject><subject>methotrexate</subject><subject>Methotrexate - administration & dosage</subject><subject>Methotrexate - pharmacokinetics</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Microscopy, Confocal</subject><subject>Neoplasm Transplantation</subject><subject>Pharmacology. Drug treatments</subject><subject>rat brain capillaries</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>tight junction</subject><subject>Tissue Distribution</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc9u1DAQxiMEokvhyhFZSHDbxU7sOLkglRVQpEpwgLM1ccapUycOdrZob30EJF6BJ-uT4P0jClw4WfL85pv55suyp4yuGC2qV7FfNf20opIKIfi9bMG4LJeiqNj9bEEplUvGquokexRjT2kqSvEwO2Fc1FLU9SL7eeautq5zW43BO-InHO3YEW_IfImkcd63tzc_mgB2JA2EYDGQ2ZM4gHMExpY4CB0S4zY-YNQ4aiQDhCsMkaSW0YdE7sF1STpn_QC3N98bhLAbE2CO-6KN3sGM7e6HHKZpmKxL6hbj4-yBARfxyfE9zb68e_t5fb68-Pj-w_rsYql5JZNTMFULLUfUdVVBWUgtAajheWmg1Olc3IBocmoKLYWWeWO0gUYYZDUy4MVp9vqgO22aAdvkZg7g1BRssrRVHqz6uzLaS9X5a8WE5IzTJPDyKBD81w3GWQ02HSXZGNFvopKM5wXjdQKf_wP2fhPGZE7lTLKaMbpTWx0gHXyMAc3vTRhVu_RV7FVKXx3TTw3P_tz_Dj_GnYAXRwCiBmcCjNrGO04UkvL95OLAfbMOt_8Zq958OueCyuIXyrjQHg</recordid><startdate>200312</startdate><enddate>200312</enddate><creator>Erdlenbruch, Bernhard</creator><creator>Alipour, Mehrnaz</creator><creator>Fricker, Gert</creator><creator>Miller, David S</creator><creator>Kugler, Wilfried</creator><creator>Eibl, Hansjörg</creator><creator>Lakomek, Max</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200312</creationdate><title>Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries</title><author>Erdlenbruch, Bernhard ; Alipour, Mehrnaz ; Fricker, Gert ; Miller, David S ; Kugler, Wilfried ; Eibl, Hansjörg ; Lakomek, Max</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4877-1af8dad4eec988a637c7aa0f426fa6c0384fa5b20f3c75c72bfcfab5fe19e1a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Alkylglycerol</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>blood–brain barrier</topic><topic>Brain - drug effects</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>brain tumor</topic><topic>Capillaries</topic><topic>confocal microscopy</topic><topic>drug delivery</topic><topic>Fluorescein</topic><topic>fluorescence markers</topic><topic>Fluorescent Dyes</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Glycerol - administration & dosage</topic><topic>Glycerol - analogs & derivatives</topic><topic>Glycerol - pharmacology</topic><topic>Injections, Intra-Arterial</topic><topic>Injections, Intraventricular</topic><topic>Male</topic><topic>Medical sciences</topic><topic>methotrexate</topic><topic>Methotrexate - administration & dosage</topic><topic>Methotrexate - pharmacokinetics</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Microscopy, Confocal</topic><topic>Neoplasm Transplantation</topic><topic>Pharmacology. Drug treatments</topic><topic>rat brain capillaries</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>tight junction</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erdlenbruch, Bernhard</creatorcontrib><creatorcontrib>Alipour, Mehrnaz</creatorcontrib><creatorcontrib>Fricker, Gert</creatorcontrib><creatorcontrib>Miller, David S</creatorcontrib><creatorcontrib>Kugler, Wilfried</creatorcontrib><creatorcontrib>Eibl, Hansjörg</creatorcontrib><creatorcontrib>Lakomek, Max</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erdlenbruch, Bernhard</au><au>Alipour, Mehrnaz</au><au>Fricker, Gert</au><au>Miller, David S</au><au>Kugler, Wilfried</au><au>Eibl, Hansjörg</au><au>Lakomek, Max</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2003-12</date><risdate>2003</risdate><volume>140</volume><issue>7</issue><spage>1201</spage><epage>1210</epage><pages>1201-1210</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>The blood–brain barrier (BBB) represents the major impediment to successful delivery of therapeutic agents to target tissue within the central nervous system. Intracarotid alkylglycerols have been shown to increase the transfer of chemotherapeutics across the BBB.
We investigated the spatial distribution of intracarotid fluorescein sodium and intravenous lissamine‐rhodamine B200 (RB 200)–albumin in the brain of normal and C6 glioma‐bearing rats after intracarotid co‐administration of 1‐O‐pentylglycerol (200 mM). To elucidate the mechanisms involved in the alkylglycerol‐mediated BBB opening, intraluminal accumulation of fluorescein isothiocyanate (FITC)–dextran 40,000 was studied in freshly isolated rat brain capillaries using confocal microscopy during incubation with different alkylglycerols. Furthermore, 1‐O‐pentylglycerol‐induced increase in delivery of methotrexate (MTX) to the brain was evaluated in nude mice.
Microscopic evaluation showed a marked 1‐O‐pentylglycerol‐induced extravasation of fluorescein and RB 200–albumin in the ipsilateral normal brain. In glioma‐bearing rats, increased tissue fluorescence was found in both tumor tissue and brain surrounding tumor. Confocal microscopy revealed a time‐ and concentration‐dependent accumulation of FITC–dextran 40,000 within the lumina of isolated rat brain capillaries during incubation with 1‐O‐pentylglycerol and 2‐O‐hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions. Intracarotid co‐administration of MTX and 1‐O‐pentylglycerol (200 mM) in nude mice resulted in a significant increase in MTX concentrations in the ipsilateral brain as compared to controls without 1‐O‐pentylglycerol (P<0.005).
In conclusion, 1‐O‐pentylglycerol increases delivery of small and large compounds to normal brain and brain tumors and this effect is mediated at least in part by enhanced permeability of tight junctions.
British Journal of Pharmacology (2003) 140, 1201–1210. doi:10.1038/sj.bjp.0705554</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>14597599</pmid><doi>10.1038/sj.bjp.0705554</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1188 |
| ispartof | British journal of pharmacology, 2003-12, Vol.140 (7), p.1201-1210 |
| issn | 0007-1188 1476-5381 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1574140 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Alkylglycerol Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacokinetics Biological and medical sciences Biomarkers, Tumor - metabolism Blood-Brain Barrier - drug effects blood–brain barrier Brain - drug effects Brain Neoplasms - metabolism Brain Neoplasms - pathology brain tumor Capillaries confocal microscopy drug delivery Fluorescein fluorescence markers Fluorescent Dyes Glioma - metabolism Glioma - pathology Glycerol - administration & dosage Glycerol - analogs & derivatives Glycerol - pharmacology Injections, Intra-Arterial Injections, Intraventricular Male Medical sciences methotrexate Methotrexate - administration & dosage Methotrexate - pharmacokinetics Mice Mice, Nude Microscopy, Confocal Neoplasm Transplantation Pharmacology. Drug treatments rat brain capillaries Rats Rats, Wistar tight junction Tissue Distribution |
| title | Alkylglycerol opening of the blood–brain barrier to small and large fluorescence markers in normal and C6 glioma‐bearing rats and isolated rat brain capillaries |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T22%3A03%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alkylglycerol%20opening%20of%20the%20blood%E2%80%93brain%20barrier%20to%20small%20and%20large%20fluorescence%20markers%20in%20normal%20and%20C6%20glioma%E2%80%90bearing%20rats%20and%20isolated%20rat%20brain%20capillaries&rft.jtitle=British%20journal%20of%20pharmacology&rft.au=Erdlenbruch,%20Bernhard&rft.date=2003-12&rft.volume=140&rft.issue=7&rft.spage=1201&rft.epage=1210&rft.pages=1201-1210&rft.issn=0007-1188&rft.eissn=1476-5381&rft.coden=BJPCBM&rft_id=info:doi/10.1038/sj.bjp.0705554&rft_dat=%3Cproquest_pubme%3E71423149%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=217191100&rft_id=info:pmid/14597599&rfr_iscdi=true |