Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: Role of the intranigral graft
Identifieur interne : 001307 ( Main/Corpus ); précédent : 001306; suivant : 001308Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: Role of the intranigral graft
Auteurs : K. Adam Baker ; Damaso Sadi ; Murray Hong ; Ivar MendezSource :
- Journal of Comparative Neurology [ 0021-9967 ] ; 2000-10-09.
English descriptors
Abstract
The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. Neurol. 426:106–116, 2000. © 2000 Wiley‐Liss, Inc.
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DOI: 10.1002/1096-9861(20001009)426:1<106::AID-CNE7>3.0.CO;2-Z
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Adam Baker</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Sadi, Damaso" sort="Sadi, Damaso" uniqKey="Sadi D" first="Damaso" last="Sadi">Damaso Sadi</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Hong, Murray" sort="Hong, Murray" uniqKey="Hong M" first="Murray" last="Hong">Murray Hong</name><affiliation><mods:affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mendez, Ivar" sort="Mendez, Ivar" uniqKey="Mendez I" first="Ivar" last="Mendez">Ivar Mendez</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:7B61DFA068A6DDF564F725AE426729213FAD1CEA</idno><date when="2000" year="2000">2000</date><idno type="doi">10.1002/1096-9861(20001009)426:1<106::AID-CNE7>3.0.CO;2-Z</idno><idno type="url">https://api.istex.fr/document/7B61DFA068A6DDF564F725AE426729213FAD1CEA/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001307</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: Role of the intranigral graft</title><author><name sortKey="Baker, K Adam" sort="Baker, K Adam" uniqKey="Baker K" first="K. 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Adam Baker</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Sadi, Damaso" sort="Sadi, Damaso" uniqKey="Sadi D" first="Damaso" last="Sadi">Damaso Sadi</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Hong, Murray" sort="Hong, Murray" uniqKey="Hong M" first="Murray" last="Hong">Murray Hong</name><affiliation><mods:affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</mods:affiliation></affiliation></author><author><name sortKey="Mendez, Ivar" sort="Mendez, Ivar" uniqKey="Mendez I" first="Ivar" last="Mendez">Ivar Mendez</name><affiliation><mods:affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Comparative Neurology</title><title level="j" type="abbrev">J. 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Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. Neurol. 426:106–116, 2000. © 2000 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>K. Adam Baker</name><affiliations><json:string>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</json:string></affiliations></json:item><json:item><name>Damaso Sadi</name><affiliations><json:string>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</json:string></affiliations></json:item><json:item><name>Murray Hong</name><affiliations><json:string>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</json:string></affiliations></json:item><json:item><name>Ivar Mendez</name><affiliations><json:string>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</json:string><json:string>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>double grafts</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>6‐hydroxydopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>reinnervation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>fetal grafts</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item></subject><articleId><json:string>CNE7</json:string></articleId><language><json:string>eng</json:string></language><abstract>The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. 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Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. 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Adam</givenNames><familyName>Baker</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Damaso</givenNames><familyName>Sadi</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Murray</givenNames><familyName>Hong</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Ivar</givenNames><familyName>Mendez</familyName></personName><contactDetails><email>mendez@is.dal.ca</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="CA" type="organization"><unparsedAffiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">double grafts</keyword><keyword xml:id="kwd2">6‐hydroxydopamine</keyword><keyword xml:id="kwd3">reinnervation</keyword><keyword xml:id="kwd4">fetal grafts</keyword><keyword xml:id="kwd5">Parkinson's disease</keyword></keywordGroup><fundingInfo><fundingAgency>QEII Health Sciences Centre</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="fr"><title type="main">Abstract</title><p>The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. Neurol. 426:106–116, 2000. © 2000 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: Role of the intranigral graft</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Role of Intranigral Graft in Double‐Grafted Rats</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: Role of the intranigral graft</title></titleInfo><name type="personal"><namePart type="given">K. Adam</namePart><namePart type="family">Baker</namePart><affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Damaso</namePart><namePart type="family">Sadi</namePart><affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Murray</namePart><namePart type="family">Hong</namePart><affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ivar</namePart><namePart type="family">Mendez</namePart><affiliation>Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</affiliation><affiliation>Division of Neurosurgery, Department of Surgery, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada</affiliation><description>Correspondence: Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2000-10-09</dateIssued><dateCaptured encoding="w3cdtf">2000-01-25</dateCaptured><dateValid encoding="w3cdtf">2000-06-21</dateValid><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">9</extent><extent unit="tables">1</extent><extent unit="references">58</extent><extent unit="words">7211</extent></physicalDescription><abstract lang="fr">The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216–7227; Mendez and Hong [1997] Brain Res 778:194–205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double‐grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double‐grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6‐OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double‐grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD. J. Comp. Neurol. 426:106–116, 2000. © 2000 Wiley‐Liss, Inc.</abstract><note type="funding">QEII Health Sciences Centre</note><subject lang="en"><genre>Keywords</genre><topic>double grafts</topic><topic>6‐hydroxydopamine</topic><topic>reinnervation</topic><topic>fetal grafts</topic><topic>Parkinson's disease</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Comparative Neurology</title></titleInfo><titleInfo type="abbreviated"><title>J. Comp. Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0021-9967</identifier><identifier type="eISSN">1096-9861</identifier><identifier type="DOI">10.1002/(ISSN)1096-9861</identifier><identifier type="PublisherID">CNE</identifier><part><date>2000</date><detail type="volume"><caption>vol.</caption><number>426</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>106</start><end>116</end><total>11</total></extent></part></relatedItem><identifier type="istex">7B61DFA068A6DDF564F725AE426729213FAD1CEA</identifier><identifier type="DOI">10.1002/1096-9861(20001009)426:1<106::AID-CNE7>3.0.CO;2-Z</identifier><identifier type="ArticleID">CNE7</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2000 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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