Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants
Protective mechanisms of the brain may reduce the extent of injury after focal cerebral ischemia. Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibi...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2007-05, Vol.27 (5), p.919-927 |
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| creator | Pignataro, Giuseppe Studer, Francesca E Wilz, Andrew Simon, Roger P Boison, Detlev |
| description | Protective mechanisms of the brain may reduce the extent of injury after focal cerebral ischemia. Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibitory neuromodulator adenosine. Embryonic stem (ES) cells, engineered to release adenosine by biallelic disruption of the adenosine kinase gene, and respective wild-type cells were induced to differentiate into either neural or glial precursor cells and were injected into the striatum of mice 1 week before middle cerebral artery occlusion. All stem cell-derived graft recipients were characterized by a significant reduction in infarct volume, an effect that was augmented by the release of adenosine. Neuroprotection was strongest in adenosine-releasing glial precursor cell recipients, which were characterized by an 85% reduction of the infarct area. Graft-mediated neuroprotection correlated with a significant improvement of general and focal neurologic scores. Histologic analysis before and after ischemia revealed clusters of implanted cells within the striatum of all treated mice. We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release. |
| doi_str_mv | 10.1038/sj.jcbfm.9600422 |
| format | Article |
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Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibitory neuromodulator adenosine. Embryonic stem (ES) cells, engineered to release adenosine by biallelic disruption of the adenosine kinase gene, and respective wild-type cells were induced to differentiate into either neural or glial precursor cells and were injected into the striatum of mice 1 week before middle cerebral artery occlusion. All stem cell-derived graft recipients were characterized by a significant reduction in infarct volume, an effect that was augmented by the release of adenosine. Neuroprotection was strongest in adenosine-releasing glial precursor cell recipients, which were characterized by an 85% reduction of the infarct area. Graft-mediated neuroprotection correlated with a significant improvement of general and focal neurologic scores. Histologic analysis before and after ischemia revealed clusters of implanted cells within the striatum of all treated mice. We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1038/sj.jcbfm.9600422</identifier><identifier>PMID: 17119544</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adenosine - metabolism ; Adenosine Kinase - genetics ; Adenosine Kinase - physiology ; Alleles ; Animals ; Biological and medical sciences ; Brain Ischemia - therapy ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Cerebral Infarction - pathology ; Cerebral Infarction - prevention & control ; Fundamental and applied biological sciences. Psychology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nervous System Diseases - pathology ; Nervous System Diseases - physiopathology ; Neurology ; Neurons - metabolism ; Neurons - transplantation ; Neuropharmacology ; Neuroprotective agent ; Pharmacology. Drug treatments ; Stem Cell Transplantation ; Vascular diseases and vascular malformations of the nervous system ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of cerebral blood flow and metabolism, 2007-05, Vol.27 (5), p.919-927</ispartof><rights>2007 ISCBFM</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-448722c89a0b0930eba41df558b72741c013e937c3e81c177b29f264b2dc74fe3</citedby><cites>FETCH-LOGICAL-c488t-448722c89a0b0930eba41df558b72741c013e937c3e81c177b29f264b2dc74fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600422$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600422$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21817,27922,27923,43619,43620</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19229569$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17119544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pignataro, Giuseppe</creatorcontrib><creatorcontrib>Studer, Francesca E</creatorcontrib><creatorcontrib>Wilz, Andrew</creatorcontrib><creatorcontrib>Simon, Roger P</creatorcontrib><creatorcontrib>Boison, Detlev</creatorcontrib><title>Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>Protective mechanisms of the brain may reduce the extent of injury after focal cerebral ischemia. Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibitory neuromodulator adenosine. Embryonic stem (ES) cells, engineered to release adenosine by biallelic disruption of the adenosine kinase gene, and respective wild-type cells were induced to differentiate into either neural or glial precursor cells and were injected into the striatum of mice 1 week before middle cerebral artery occlusion. All stem cell-derived graft recipients were characterized by a significant reduction in infarct volume, an effect that was augmented by the release of adenosine. Neuroprotection was strongest in adenosine-releasing glial precursor cell recipients, which were characterized by an 85% reduction of the infarct area. Graft-mediated neuroprotection correlated with a significant improvement of general and focal neurologic scores. Histologic analysis before and after ischemia revealed clusters of implanted cells within the striatum of all treated mice. We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release.</description><subject>Adenosine - metabolism</subject><subject>Adenosine Kinase - genetics</subject><subject>Adenosine Kinase - physiology</subject><subject>Alleles</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain Ischemia - therapy</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Cerebral Infarction - pathology</subject><subject>Cerebral Infarction - prevention & control</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nervous System Diseases - pathology</subject><subject>Nervous System Diseases - physiopathology</subject><subject>Neurology</subject><subject>Neurons - metabolism</subject><subject>Neurons - transplantation</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Pharmacology. Drug treatments</subject><subject>Stem Cell Transplantation</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</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><recordid>eNp9kUtr3TAQhUVJaG7S7rtpMYUkK99Ksp7LEPKCkCzaQndCkseJjR83kl3Iv49u7PZCFgGBYPTN0Zk5CH0heE1woX7EZt14V3VrLTBmlH5AK8K5ziUmYg-tMJUkF1L9OUCHMTYYY1Vw_hEdEEmI5oyt0M87mMKwCcMIfqyHPqvTif4Rutpn3TBFyFyw22JfTh7KzD1ncYQu89C2eQmh_rstzki3aW0_xk9ov7JthM_LfYR-X178Or_Ob--vbs7PbnPPlBpzxpSk1CttscO6wOAsI2XFuXKSSkY8JgXoQvoCFPFESkd1RQVztPSSVVAcodNZN9l_miCOpkvWky_bQ3JulBSUcUFFIk_eJSVmpFBCJfD7G7AZptCnKQxNGyNSv6rhGfJhiDFAZTah7mx4NgSbbS4mNuY1F7Pkklq-LbqT66DcNSxBJOB4AWz0tq2C7X0dd5ymVHOhE5fPXLQPsDP3zsdfZ7634xTgv-C_9xf9-68I</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Pignataro, Giuseppe</creator><creator>Studer, Francesca E</creator><creator>Wilz, Andrew</creator><creator>Simon, Roger P</creator><creator>Boison, Detlev</creator><general>SAGE Publications</general><general>Lippincott Williams & Wilkins</general><general>Sage Publications Ltd</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>7X7</scope><scope>7XB</scope><scope>88A</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20070501</creationdate><title>Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants</title><author>Pignataro, Giuseppe ; Studer, Francesca E ; Wilz, Andrew ; Simon, Roger P ; Boison, Detlev</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-448722c89a0b0930eba41df558b72741c013e937c3e81c177b29f264b2dc74fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenosine - metabolism</topic><topic>Adenosine Kinase - genetics</topic><topic>Adenosine Kinase - physiology</topic><topic>Alleles</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - therapy</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Cerebral Infarction - pathology</topic><topic>Cerebral Infarction - prevention & control</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nervous System Diseases - pathology</topic><topic>Nervous System Diseases - physiopathology</topic><topic>Neurology</topic><topic>Neurons - metabolism</topic><topic>Neurons - transplantation</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Pharmacology. Drug treatments</topic><topic>Stem Cell Transplantation</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pignataro, Giuseppe</creatorcontrib><creatorcontrib>Studer, Francesca E</creatorcontrib><creatorcontrib>Wilz, Andrew</creatorcontrib><creatorcontrib>Simon, Roger P</creatorcontrib><creatorcontrib>Boison, Detlev</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</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>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>Neurosciences Abstracts</collection><jtitle>Journal of cerebral blood flow and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pignataro, Giuseppe</au><au>Studer, Francesca E</au><au>Wilz, Andrew</au><au>Simon, Roger P</au><au>Boison, Detlev</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants</atitle><jtitle>Journal of cerebral blood flow and metabolism</jtitle><addtitle>J Cereb Blood Flow Metab</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>27</volume><issue>5</issue><spage>919</spage><epage>927</epage><pages>919-927</pages><issn>0271-678X</issn><eissn>1559-7016</eissn><coden>JCBMDN</coden><abstract>Protective mechanisms of the brain may reduce the extent of injury after focal cerebral ischemia. Here, we explored in a mouse model of focal cerebral ischemia potential synergistic neuroprotective effects of two mediators of neuroprotection: (i) neuronal or glial precursor cells and (ii) the inhibitory neuromodulator adenosine. Embryonic stem (ES) cells, engineered to release adenosine by biallelic disruption of the adenosine kinase gene, and respective wild-type cells were induced to differentiate into either neural or glial precursor cells and were injected into the striatum of mice 1 week before middle cerebral artery occlusion. All stem cell-derived graft recipients were characterized by a significant reduction in infarct volume, an effect that was augmented by the release of adenosine. Neuroprotection was strongest in adenosine-releasing glial precursor cell recipients, which were characterized by an 85% reduction of the infarct area. Graft-mediated neuroprotection correlated with a significant improvement of general and focal neurologic scores. Histologic analysis before and after ischemia revealed clusters of implanted cells within the striatum of all treated mice. We conclude that ES cell derived adenosine-releasing brain implants provide neuroprotection by synergism of endogenous precursor cell-mediated effects and paracrine adenosine release.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>17119544</pmid><doi>10.1038/sj.jcbfm.9600422</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine - metabolism Adenosine Kinase - genetics Adenosine Kinase - physiology Alleles Animals Biological and medical sciences Brain Ischemia - therapy Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebral Infarction - pathology Cerebral Infarction - prevention & control Fundamental and applied biological sciences. Psychology Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Nervous System Diseases - pathology Nervous System Diseases - physiopathology Neurology Neurons - metabolism Neurons - transplantation Neuropharmacology Neuroprotective agent Pharmacology. Drug treatments Stem Cell Transplantation Vascular diseases and vascular malformations of the nervous system Vertebrates: nervous system and sense organs |
| title | Neuroprotection in ischemic mouse brain induced by stem cell-derived brain implants |
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