A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology
Identifieur interne : 001D09 ( Main/Corpus ); précédent : 001D08; suivant : 001D10A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology
Auteurs : G. Nikkhah ; M. Olsson ; J. Eberhard ; C. Bentlage ; M. G. Cunningham ; A. Bjo RklundSource :
- Neuroscience [ 0306-4522 ] ; 1994.
English descriptors
Abstract
Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhahet al. (1994)Brain Res.633, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991)Neuron6, 1–12].
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DOI: 10.1016/0306-4522(94)90007-8
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Eberhard</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Bentlage, C" sort="Bentlage, C" uniqKey="Bentlage C" first="C." last="Bentlage">C. Bentlage</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Cunningham, M G" sort="Cunningham, M G" uniqKey="Cunningham M" first="M. G." last="Cunningham">M. G. Cunningham</name><affiliation><mods:affiliation>Harvard Medical School, Boston, MA 02115, U.S.A.</mods:affiliation></affiliation></author><author><name sortKey="Bjo Rklund, A" sort="Bjo Rklund, A" uniqKey="Bjo Rklund A" first="A." last="Bjo Rklund">A. 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Nikkhah</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Olsson, M" sort="Olsson, M" uniqKey="Olsson M" first="M." last="Olsson">M. Olsson</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Eberhard, J" sort="Eberhard, J" uniqKey="Eberhard J" first="J." last="Eberhard">J. Eberhard</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Bentlage, C" sort="Bentlage, C" uniqKey="Bentlage C" first="C." last="Bentlage">C. Bentlage</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Cunningham, M G" sort="Cunningham, M G" uniqKey="Cunningham M" first="M. G." last="Cunningham">M. G. Cunningham</name><affiliation><mods:affiliation>Harvard Medical School, Boston, MA 02115, U.S.A.</mods:affiliation></affiliation></author><author><name sortKey="Bjo Rklund, A" sort="Bjo Rklund, A" uniqKey="Bjo Rklund A" first="A." last="Bjo Rklund">A. Bjo Rklund</name><affiliation><mods:affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Neuroscience</title><title level="j" type="abbrev">NSC</title><idno type="ISSN">0306-4522</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994">1994</date><biblScope unit="volume">63</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="57">57</biblScope><biblScope unit="page" to="72">72</biblScope></imprint><idno type="ISSN">0306-4522</idno></series><idno type="istex">529812786D9C6610FCB69624D9E40A3D7F6A2EE7</idno><idno type="DOI">10.1016/0306-4522(94)90007-8</idno><idno type="PII">0306-4522(94)90007-8</idno><idno type="ArticleID">94900078</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>6-OHDA</term><term>DAB</term><term>DARPP-32</term><term>DMEM</term><term>GFAP</term><term>PB</term><term>TH</term><term>VM</term><term>o.d.</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhahet al. (1994)Brain Res.633, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991)Neuron6, 1–12].</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>G. 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Bjo¨rklund</name><affiliations><json:string>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>DAB : 3,3′diaminobenzidine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DARPP-32 : dopamine- and adenosine-3′-5′-monophosphate-regulated phosphoprotein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DMEM : Dulbecco's minimum essential medium</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GFAP : glial fibrillary acidic protein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>o.d. : outer diameter</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>6-OHDA : 6-hydroxydopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PB : phosphate buffer</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TH : tyrosine hydroxylase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>VM : ventral mesencephalon</value></json:item></subject><articleId><json:string>94900078</json:string></articleId><language><json:string>eng</json:string></language><abstract>Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhahet al. (1994)Brain Res.633, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991)Neuron6, 1–12].</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>504 x 756 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>9</keywordCount><abstractCharCount>2817</abstractCharCount><pdfWordCount>8007</pdfWordCount><pdfCharCount>50832</pdfCharCount><pdfPageCount>16</pdfPageCount><abstractWordCount>387</abstractWordCount></qualityIndicators><title>A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the 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Sweden</affiliation></author><author><persName><forename type="first">M.</forename><surname>Olsson</surname></persName><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation></author><author><persName><forename type="first">J.</forename><surname>Eberhard</surname></persName><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation></author><author><persName><forename type="first">C.</forename><surname>Bentlage</surname></persName><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation></author><author><persName><forename type="first">M.G.</forename><surname>Cunningham</surname></persName><affiliation>Harvard Medical School, Boston, MA 02115, U.S.A.</affiliation></author><author><persName><forename type="first">A.</forename><surname>Bjo¨rklund</surname></persName><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation></author></analytic><monogr><title level="j">Neuroscience</title><title level="j" type="abbrev">NSC</title><idno type="pISSN">0306-4522</idno><idno type="PII">S0306-4522(00)X0304-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994"></date><biblScope unit="volume">63</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="57">57</biblScope><biblScope unit="page" to="72">72</biblScope></imprint></monogr><idno type="istex">529812786D9C6610FCB69624D9E40A3D7F6A2EE7</idno><idno type="DOI">10.1016/0306-4522(94)90007-8</idno><idno type="PII">0306-4522(94)90007-8</idno><idno type="ArticleID">94900078</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhahet al. (1994)Brain Res.633, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991)Neuron6, 1–12].</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><item><term>DAB</term><term>3,3′diaminobenzidine</term></item><item><term>DARPP-32</term><term>dopamine- and adenosine-3′-5′-monophosphate-regulated phosphoprotein</term></item><item><term>DMEM</term><term>Dulbecco's minimum essential medium</term></item><item><term>GFAP</term><term>glial fibrillary acidic protein</term></item><item><term>o.d.</term><term>outer diameter</term></item><item><term>6-OHDA</term><term>6-hydroxydopamine</term></item><item><term>PB</term><term>phosphate buffer</term></item><item><term>TH</term><term>tyrosine hydroxylase</term></item><item><term>VM</term><term>ventral mesencephalon</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1994-05-07">Registration</change><change when="1994">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"></istex:docType><istex:document><article version="5.0" xml:lang="en" docsubtype="fla"><item-info><jid>NSC</jid><aid>94900078</aid><ce:pii>0306-4522(94)90007-8</ce:pii><ce:doi>10.1016/0306-4522(94)90007-8</ce:doi><ce:copyright type="unknown" year="1994">IBRO</ce:copyright></item-info><head><ce:title>A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology</ce:title><ce:author-group><ce:author><ce:given-name>G.</ce:given-name><ce:surname>Nikkhah</ce:surname><ce:cross-ref refid="cor1"><ce:sup>‡</ce:sup></ce:cross-ref><ce:cross-ref refid="aff1"><ce:sup>*</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>†</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>M.</ce:given-name><ce:surname>Olsson</ce:surname><ce:cross-ref refid="aff1"><ce:sup>*</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>J.</ce:given-name><ce:surname>Eberhard</ce:surname><ce:cross-ref refid="aff1"><ce:sup>*</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>C.</ce:given-name><ce:surname>Bentlage</ce:surname><ce:cross-ref refid="aff1"><ce:sup>*</ce:sup></ce:cross-ref><ce:cross-ref refid="aff2"><ce:sup>†</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>M.G.</ce:given-name><ce:surname>Cunningham</ce:surname><ce:cross-ref refid="aff3"><ce:sup>§</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>A.</ce:given-name><ce:surname>Bjo¨rklund</ce:surname><ce:cross-ref refid="aff1"><ce:sup>*</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="aff1"><ce:label>*</ce:label><ce:textfn>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</ce:textfn></ce:affiliation><ce:affiliation id="aff2"><ce:label>†</ce:label><ce:textfn>Neurosurgical clinic, Nordstadt Hospital, Haltenhoffstr. 41, D-30167 Hannover, Germany</ce:textfn></ce:affiliation><ce:affiliation id="aff3"><ce:label>§</ce:label><ce:textfn>Harvard Medical School, Boston, MA 02115, U.S.A.</ce:textfn></ce:affiliation><ce:correspondence id="cor1"><ce:label>‡</ce:label><ce:text>To whom all correspondence should be addressed.</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="7" month="5" year="1994"></ce:date-accepted><ce:abstract id="ab1" class="author" xml:lang="en"><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [<ce:cross-ref refid="bib29">Nikkhah<ce:italic>et al.</ce:italic> (1994)</ce:cross-ref><ce:italic>Brain Res</ce:italic>.<ce:bold>633</ce:bold>, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.</ce:simple-para><ce:simple-para>The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [<ce:cross-ref refid="bib19">Gage and Fisher (1991)</ce:cross-ref><ce:italic>Neuron</ce:italic><ce:bold>6</ce:bold>, 1–12].</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="abr" xml:lang="en"><ce:keyword><ce:text>DAB</ce:text><ce:keyword><ce:text>3,3′diaminobenzidine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>DARPP-32</ce:text><ce:keyword><ce:text>dopamine- and adenosine-3′-5′-monophosphate-regulated phosphoprotein</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>DMEM</ce:text><ce:keyword><ce:text>Dulbecco's minimum essential medium</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>GFAP</ce:text><ce:keyword><ce:text>glial fibrillary acidic protein</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>o.d.</ce:text><ce:keyword><ce:text>outer diameter</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>6-OHDA</ce:text><ce:keyword><ce:text>6-hydroxydopamine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PB</ce:text><ce:keyword><ce:text>phosphate buffer</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TH</ce:text><ce:keyword><ce:text>tyrosine hydroxylase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>VM</ce:text><ce:keyword><ce:text>ventral mesencephalon</ce:text></ce:keyword></ce:keyword></ce:keywords></head><tail><ce:bibliography><ce:section-title>References</ce:section-title><ce:bibliography-sec><ce:bib-reference id="bib1"><ce:label>1.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Abercrombie</ce:surname><ce:given-name>M.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Estimation of nuclear population from microtome sections</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Anat. 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1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>New Engl. J. Med.</sb:maintitle></sb:title><sb:volume-nr>327</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>1556</sb:first-page><sb:last-page>1563</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>A microtransplantation approach for cell suspension grafting in the rat parkinson model: A detailed account of the methodology</title></titleInfo><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Nikkhah</namePart><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation><description>To whom all correspondence should be addressed.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Olsson</namePart><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.</namePart><namePart type="family">Eberhard</namePart><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Bentlage</namePart><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.G.</namePart><namePart type="family">Cunningham</namePart><affiliation>Harvard Medical School, Boston, MA 02115, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Bjo¨rklund</namePart><affiliation>Department of Medical Cell Research, University of Lund, Biskopsgatan 5, S-223 62 Lund, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued><dateValid encoding="w3cdtf">1994-05-07</dateValid><copyrightDate encoding="w3cdtf">1994</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesen-cephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhahet al. (1994)Brain Res.633, 133–143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 μl along four injection tracts (150,000 cells/μl) using either a glass capillary (o.d. 50–70 μm) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000–75,000 cells in 0.5 μl, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000–35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum.The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991)Neuron6, 1–12].</abstract><subject lang="en"><topic>DAB : 3,3′diaminobenzidine</topic><topic>DARPP-32 : dopamine- and adenosine-3′-5′-monophosphate-regulated phosphoprotein</topic><topic>DMEM : Dulbecco's minimum essential medium</topic><topic>GFAP : glial fibrillary acidic protein</topic><topic>o.d. : outer diameter</topic><topic>6-OHDA : 6-hydroxydopamine</topic><topic>PB : phosphate buffer</topic><topic>TH : tyrosine hydroxylase</topic><topic>VM : ventral mesencephalon</topic></subject><relatedItem type="host"><titleInfo><title>Neuroscience</title></titleInfo><titleInfo type="abbreviated"><title>NSC</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199411</dateIssued></originInfo><identifier type="ISSN">0306-4522</identifier><identifier type="PII">S0306-4522(00)X0304-1</identifier><part><detail type="volume"><number>63</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>350</end></extent><extent unit="pages"><start>57</start><end>72</end></extent></part></relatedItem><identifier type="istex">529812786D9C6610FCB69624D9E40A3D7F6A2EE7</identifier><identifier type="DOI">10.1016/0306-4522(94)90007-8</identifier><identifier type="PII">0306-4522(94)90007-8</identifier><identifier type="ArticleID">94900078</identifier><accessCondition type="use and reproduction" contentType="">© 1994IBRO</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>IBRO, ©1994</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/529812786D9C6610FCB69624D9E40A3D7F6A2EE7/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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