2001
Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease
Collier TJ, Sortwell CE, Elsworth JD, Taylor JR, Roth RH, Sladek JR, Redmond DE. Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease. The Journal Of Comparative Neurology 2001, 442: 320-330. PMID: 11793337, DOI: 10.1002/cne.10108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrain Tissue TransplantationCell DifferentiationChlorocebus aethiopsDopamineGraft SurvivalHomovanillic AcidImmunohistochemistryMaleNeostriatumNerve RegenerationNeuritesNeuronsParkinsonian DisordersRecovery of FunctionStem Cell TransplantationStem CellsSubstantia NigraTreatment OutcomeTyrosine 3-MonooxygenaseConceptsSubstantia nigraParkinson's diseaseDA neuronsVentral mesencephalonTyrosine hydroxylaseTH-positive fiber densityEmbryonic DA neuronsEmbryonic dopamine neuronsRostral substantia nigraStriatal DA depletionVentral mesencephalic graftsBasal ganglia circuitryBasal ganglia structuresSuboptimal therapeutic outcomesAfrican green monkeysDA modulationGrafted neuronsVM graftsMesencephalic graftsParkinsonian monkeysSN neuronsDA depletionReplacement therapyDA replacementDA levels
2000
Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: evidence for cognitive impulsivity
Jentsch J, Roth R, Taylor J. Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: evidence for cognitive impulsivity. Biological Psychiatry 2000, 48: 415-424. PMID: 10978725, DOI: 10.1016/s0006-3223(00)00926-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChlorocebus aethiopsCognitionConditioning, OperantFemaleHallucinogensImpulsive BehaviorMaleMental RecallPhencyclidineConceptsPhencyclidine administrationObject retrieval detour taskFrontal cortical dysfunctionFrontal cortex ablationSubchronic phencyclidine administrationPerformance of trialsDrugs of abusePhencyclidine exposureSubchronic administrationIntermittent administrationCortical dysfunctionDrug withdrawalChronic consumptionDopaminergic dysfunctionBehavioral deficitsPsychotomimetic drugsCorticostriatal functionInhibitory response controlCognitive impairmentImpaired acquisitionNonhuman primatesAdministrationPhencyclidineDysfunctionInhibitory control
1999
Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment
Elsworth J, Taylor J, Sladek J, Collier T, Redmond D, Roth R. Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment. Neuroscience 1999, 95: 399-408. PMID: 10658619, DOI: 10.1016/s0306-4522(99)00437-6.Peer-Reviewed Original ResearchConceptsHomovanillic acid/dopamine ratioMPTP treatmentStriatal dopamine levelsDopamine levelsDopamine lossDopamine depletionDopamine ratioStriatal subregionsNucleus accumbensCaudate nucleusDopamine concentrationsOne-yearSeverity categoriesDopamine neuron integrityVentromedial caudate nucleusStriatal dopamine lossHomovanillic acid concentrationsStriatal dopaminergic functionMarked increaseNormal motor performancePaucity of dataMetabolic activityNon-human primatesParkinsonian disabilityTetrahydropyridine (MPTP) modelSpontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys
Taylor J, Elsworth J, Lawrence M, Sladek J, Roth R, Redmond D. Spontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys. Experimental Neurology 1999, 158: 214-220. PMID: 10448434, DOI: 10.1006/exnr.1999.7093.Peer-Reviewed Original ResearchConceptsCaudate nucleusConcentration of DAEye blink rateBlink rateDA ratioDopaminergic regulationD1 agonist dihydrexidineDA D2 receptorsDopaminergic neurotoxin MPTPSeverity of parkinsonismSpontaneous eye blink rateSpecific brain regionsAntiparkinsonian effectsDA depletionD2 agonistDopamine D1Dopamine levelsNeurotoxin MPTPD2 receptorsMPTPNormal animalsRostral portionSubcortical regionsBrain regionsVentromedial regionAltered frontal cortical dopaminergic transmission in monkeys after subchronic phencyclidine exposure: involvement in frontostriatal cognitive deficits
Jentsch J, Taylor J, Elsworth J, Redmond D, Roth R. Altered frontal cortical dopaminergic transmission in monkeys after subchronic phencyclidine exposure: involvement in frontostriatal cognitive deficits. Neuroscience 1999, 90: 823-832. PMID: 10218783, DOI: 10.1016/s0306-4522(98)00481-3.Peer-Reviewed Original ResearchConceptsCognitive deficitsSubchronic phencyclidine administrationDorsolateral prefrontal cortexFrontal cortexCortical dopamine transmissionReduced dopaminergic functionFrontostriatal functionDetour taskCognitive performanceDopamine utilizationPhencyclidine exposurePrefrontal cortexPerformance impairmentPrelimbic cortexBrain regionsCognitive dysfunctionCortical impairmentCortical regionsCognitive impairmentDopaminergic functionPhencyclidine administrationDopamine transmissionSpecific subregionsCortexPsychotomimetic drug phencyclidineDopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys
Jentsch J, Taylor J, Redmond Jr D, Elsworth J, Youngren K, Roth R. Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys. Psychopharmacology 1999, 142: 78-84. PMID: 10102786, DOI: 10.1007/s002130050865.Peer-Reviewed Original ResearchConceptsFrontostriatal systemCognitive functionPrefrontal cortexObject retrieval taskRegulation of cognitionPrimate prefrontal cortexD4 dopamine receptorsNormal control monkeysDR antagonistsCognitive processesDetour taskCognitive deficitsPerformance impairmentBrain regionsCognitive dysfunctionRetrieval tasksFrontal cortexTaskCortexCortical dopaminergicDeficitsDopaminergic systemAntagonist reversalControl subjectsDopamine receptors
1998
In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector
During M, Samulski R, Elsworth J, Kaplitt M, Leone P, Xiao X, Li J, Freese A, Taylor J, Roth R, Sladek J, O’Malley K, Redmond D. In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Therapy 1998, 5: 820-827. PMID: 9747462, DOI: 10.1038/sj.gt.3300650.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAromatic-L-Amino-Acid DecarboxylasesChlorocebus aethiopsDependovirusDopamineDopamine AgentsGene ExpressionGene Transfer TechniquesGenetic VectorsHumansImmunohistochemistryMaleParkinson DiseaseTrigeminal Caudal NucleusTyrosine 3-MonooxygenaseConceptsTyrosine hydroxylaseStriatal cellsDopamine-depleted monkeysAdeno-associated virus vectorProduction of dopamineParkinsonian monkeysTransient feverSevere hyperactivityStriatal dopaminePrimate neuronsStereotactic injectionHistological evidencePrimate modelInjection tractNeurotoxin MPTPDopamine productionParkinson's diseaseTreatment groupsSignificant toxicityBehavioral effectsVivo gene therapyElevated levelsBiochemical effectsFirst dayMonkeysUpregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study
Elsworth J, Brittan M, Taylor J, Sladek J, Redmond D, Innis R, Zea-Ponce Y, Roth R. Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study. Brain Research 1998, 795: 55-62. PMID: 9622593, DOI: 10.1016/s0006-8993(98)00252-2.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAutoradiographyBenzofuransBrain Tissue TransplantationChlorocebus aethiopsCorpus StriatumDisease Models, AnimalDopamine AgentsFetal Tissue TransplantationImage Processing, Computer-AssistedIodine RadioisotopesMesencephalonParkinson Disease, SecondaryRadioligand AssayReceptors, Dopamine D2Up-RegulationConceptsFetal ventral mesencephalonD2 receptor bindingVentral mesencephalonDorsal striatumAutoradiographic studyDopamine uptake site densityPostsynaptic dopamine receptor activationVentral striatumDopamine concentrationsStriatal D2 receptor bindingReceptor bindingD2 receptor upregulationPostsynaptic dopamine transmissionTetrahydropyridine-treated monkeysStriatal D2 receptorsDopamine receptor activationPrevious autoradiographic studiesAfrican green monkeysDonor neuronsIntrastriatal graftingParkinsonian primatesNeural transplantationReceptor upregulationStriatal circuitryMotor functionIntrastriatal Grafts From Multiple Donors Do Not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates
Sladek J, Collier T, Elsworth J, Roth R, Taylor J, Redmond D. Intrastriatal Grafts From Multiple Donors Do Not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates. Cell Transplantation 1998, 7: 87-96. DOI: 10.1016/s0963-6897(98)00007-4.Peer-Reviewed Original ResearchConceptsDopamine neuronsDouble graftsAdult African green monkeysVentral mesencephalic dopamine neuronsMultiple donorsGrafts of tissueMore dopamine neuronsSymptoms of parkinsonismMesencephalic dopamine neuronsDopamine cell survivalHuman clinical trialsAfrican green monkeysIntrastriatal graftsPositive neuronsTotal numberClinical trialsDopamine levelsCaudate nucleusRecipient animalsGraftGrafted tissueNeuronsGreen monkeysNonhuman primatesDorsoventral extentIntrastriatal Grafts from Multiple Donors do not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates
Sladek J, Collier T, Elsworth J, Roth R, Taylor J, Redmond D. Intrastriatal Grafts from Multiple Donors do not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates. Cell Transplantation 1998, 7: 87-96. PMID: 9588591, DOI: 10.1177/096368979800700204.Peer-Reviewed Original ResearchConceptsDopamine neuronsDouble graftsAdult African green monkeysVentral mesencephalic dopamine neuronsMultiple donorsGrafts of tissueMore dopamine neuronsSymptoms of parkinsonismMesencephalic dopamine neuronsDopamine cell survivalHuman clinical trialsAfrican green monkeysIntrastriatal graftsPositive neuronsTotal numberClinical trialsDopamine levelsCaudate nucleusRecipient animalsGraftGrafted tissueNeuronsGreen monkeysNonhuman primatesDorsoventral extent
1997
Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus)
Taylor J, Elsworth J, Roth R, Sladek J, Redmond D. Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus). Neuroscience 1997, 81: 745-755. PMID: 9316026, DOI: 10.1016/s0306-4522(97)00214-5.Peer-Reviewed Original ResearchConceptsParkinson's diseaseSevere parkinsonismAdult male African green monkeysMale African green monkeysTetrahydropyridine-induced parkinsonismMPTP-induced parkinsonismIdiopathic Parkinson's diseaseNovel therapeutic treatmentsLong-term deficitsAfrican green monkeysGroups of animalsNon-human primatesMPTP treatmentParkinsonian monkeysMPTP administrationVervet monkeysFunctional deficitsInitial severityStable parkinsonismBehavioral deficitsAnimal modelsParkinsonismParkinsonian subjectsMPTPTherapeutic treatmentEnduring Cognitive Deficits and Cortical Dopamine Dysfunction in Monkeys After Long-Term Administration of Phencyclidine
Jentsch J, Redmond D, Elsworth J, Taylor J, Youngren K, Roth R. Enduring Cognitive Deficits and Cortical Dopamine Dysfunction in Monkeys After Long-Term Administration of Phencyclidine. Science 1997, 277: 953-955. PMID: 9252326, DOI: 10.1126/science.277.5328.953.Peer-Reviewed Original ResearchConceptsDopamine utilizationPrefrontal cortexAtypical antipsychotic drug clozapineLong-term administrationDirect drug effectAntipsychotic drug clozapinePsychotomimetic drug phencyclidineAdministration of phencyclidineDorsolateral prefrontal cortexDopamine hypofunctionPrefrontal cortex functionCognitive dysfunctionPhencyclidine treatmentBehavioral deficitsDopamine dysfunctionPsychiatric disordersDrug effectsDrug clozapineDrug phencyclidineBrain regionsCognitive deficitsCortex functionCognitive functionPhencyclidineCortexMetabolic energy capacity of dopaminergic grafts and the implanted striatum in parkinsonian nonhuman primates as visualized with cytochrome oxidase histochemistry
Collier T, Redmond D, Roth R, Elsworth J, Taylor J, Sladek J. Metabolic energy capacity of dopaminergic grafts and the implanted striatum in parkinsonian nonhuman primates as visualized with cytochrome oxidase histochemistry. Cell Transplantation 1997, 6: 135-140. DOI: 10.1016/s0963-6897(97)00003-1.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsBrain Tissue TransplantationChlorocebus aethiopsCorpus StriatumDopamineElectron Transport Complex IVEnergy MetabolismFetal Tissue TransplantationGestational AgeImmunohistochemistryMesencephalonNeuronsParkinson Disease, SecondaryTyrosine 3-MonooxygenaseConceptsDA neuronsEmbryonic ventral mesencephalic tissueParkinsonian nonhuman primatesStriatum of DATyrosine hydroxylase immunocytochemistryVentral mesencephalic tissueVentral mesencephalic graftsCytochrome oxidase histochemistryCytochrome oxidase stainingMitochondrial enzyme cytochrome oxidaseLocal energy metabolismActive innervationBilateral graftsNeuron contentDopaminergic graftsMesencephalic graftsMesencephalic tissueHost brainBrain metabolismEnzyme cytochrome oxidaseCO stainingTissue transplantsGraftMetabolic activityNonhuman primatesMetabolic Energy Capacity of Dopaminergic Grafts and the Implanted Striatum in Parkinsonian Nonhuman Primates as Visualized with Cytochrome Oxidase Histochemistry
Collier T, Redmond D, Roth R, Elsworth J, Taylor J, Sladek J. Metabolic Energy Capacity of Dopaminergic Grafts and the Implanted Striatum in Parkinsonian Nonhuman Primates as Visualized with Cytochrome Oxidase Histochemistry. Cell Transplantation 1997, 6: 135-140. PMID: 9142445, DOI: 10.1177/096368979700600207.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsBrain Tissue TransplantationChlorocebus aethiopsCorpus StriatumDopamineElectron Transport Complex IVEnergy MetabolismFetal Tissue TransplantationGestational AgeImmunohistochemistryMesencephalonNeuronsParkinson Disease, SecondaryTyrosine 3-MonooxygenaseConceptsDA neuronsEmbryonic ventral mesencephalic tissueParkinsonian nonhuman primatesStriatum of DATyrosine hydroxylase immunocytochemistryVentral mesencephalic tissueVentral mesencephalic graftsBrain energy metabolismCytochrome oxidase histochemistryCytochrome oxidase stainingMitochondrial enzyme cytochrome oxidaseLocal energy metabolismEnergy metabolismActive innervationBilateral graftsNeuron contentDopaminergic graftsMesencephalic graftsMesencephalic tissueHost brainEnzyme cytochrome oxidaseCO stainingTissue transplantsGraftMetabolic activity
1996
Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys
Elsworth J, Sladek J, Taylor J, Collier T, Redmond D, Roth R. Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys. Neuroscience 1996, 72: 477-484. PMID: 8737417, DOI: 10.1016/0306-4522(95)00564-1.Peer-Reviewed Original ResearchConceptsFetal ventral mesencephalonVentral mesencephalonCaudate nucleusGraft siteDopamine neuronsDopamine concentrationsBehavioral recoveryTyrosine hydroxylase-positive neuronsHomovanillic acid/dopamine ratioFetal dopamine neuronsGrafted dopamine neuronsIntrastriatal transplantsParkinsonian primatesGrafted neuronsIntrastriatal transplantationGestational ageTransplant proceduresDopamine ratioDopamine productionSignificant elevationNucleus accumbensDopamine systemSham graftsGraftBrain regionsRestoration of dopamine transporter density in the striatum of fetal ventral mesencephalon-grafted, but not sham-grafted, MPTP-treated parkinsonian monkeys
Elsworth J, Brittan M, Taylor J, Sladek J, Al-Tikriti M, Zea-Ponce Y, Innis R, Redmond D, Roth R. Restoration of dopamine transporter density in the striatum of fetal ventral mesencephalon-grafted, but not sham-grafted, MPTP-treated parkinsonian monkeys. Cell Transplantation 1996, 5: 315-325. DOI: 10.1016/0963-6897(95)02034-9.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAutoradiographyBrain Tissue TransplantationCarrier ProteinsChlorocebus aethiopsCocaineDopamineDopamine Plasma Membrane Transport ProteinsFetal Tissue TransplantationHomovanillic AcidIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMesencephalonNeostriatumNerve Tissue ProteinsParkinson Disease, SecondaryProtein BindingPutamenConceptsFetal dopamine neuronsDopamine transporter densityDopamine neuronsParkinsonian monkeysBehavioral recoveryTransporter densityCaudate nucleusNeural graftingDopamine systemImplantation procedureDopamine concentrationsFull behavioral recoveryPutamen of MPTPStriatal dopamine deficiencyStriatal dopamine concentrationsDopamine-depleted striatumStriatum of MPTPDopamine depletionVentral mesencephalonDopamine deficiencyMotor abnormalitiesDopaminergic innervationUseful treatmentStriatal nucleiAdult striatumRestoration of Dopamine Transporter Density in the Striatum of Fetal Ventral Mesencephalon-Grafted, but not Sham-Grafted, Mptp-Treated Parkinsonian Monkeys
Elsworth J, Brittan M, Taylor J, Sladek J, Al-Tikriti M, Zea-Ponce Y, Innis R, Redmond D, Roth R. Restoration of Dopamine Transporter Density in the Striatum of Fetal Ventral Mesencephalon-Grafted, but not Sham-Grafted, Mptp-Treated Parkinsonian Monkeys. Cell Transplantation 1996, 5: 315-325. PMID: 8689042, DOI: 10.1177/096368979600500220.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAutoradiographyBrain Tissue TransplantationCarrier ProteinsChlorocebus aethiopsCocaineDopamineDopamine Plasma Membrane Transport ProteinsFetal Tissue TransplantationHomovanillic AcidIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMesencephalonNeostriatumNerve Tissue ProteinsParkinson Disease, SecondaryProtein BindingPutamenConceptsFetal dopamine neuronsDopamine transporter densityDopamine neuronsParkinsonian monkeysBehavioral recoveryTransporter densityCaudate nucleusNeural graftingDopamine systemImplantation procedureDopamine concentrationsFull behavioral recoveryPutamen of MPTPStriatal dopamine deficiencyStriatal dopamine concentrationsDopamine-depleted striatumStriatum of MPTPDopamine depletionVentral mesencephalonDopamine deficiencyMotor abnormalitiesDopaminergic innervationUseful treatmentStriatal nucleiAdult striatum
1995
Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys
Taylor J, Elsworth J, Sladek J, Collier T, Roth R, Redmond D. Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys. Cell Transplantation 1995, 4: 13-26. DOI: 10.1016/0963-6897(94)00035-i.Peer-Reviewed Original ResearchConceptsFetal mesencephalic tissueSubstantia nigra graftsSham surgeryBehavioral improvementMesencephalic tissueBehavioral deficitsAdult male African green monkeysDopamine concentrationsMale African green monkeysFetal dopamine neuronsSystemic MPTP administrationIdiopathic Parkinson's diseaseStriatum of MPTPSham-operated monkeysPostmortem brain tissueAfrican green monkeysMore variable effectsNeuronal synaptic connectionsHost neuronsHost striatumHost brainMPTP administrationGestational ageSubstantia nigraNeuronal effectsSham Surgery does not Ameliorate MPTP-Induced Behavioral Deficits in Monkeys
Taylor J, Elsworth J, Sladek J, Collier T, Roth R, Redmond D. Sham Surgery does not Ameliorate MPTP-Induced Behavioral Deficits in Monkeys. Cell Transplantation 1995, 4: 13-26. PMID: 7728327, DOI: 10.1177/096368979500400105.Peer-Reviewed Original ResearchConceptsFetal mesencephalic tissueSubstantia nigra graftsSham surgeryBehavioral improvementMesencephalic tissueBehavioral deficitsAdult male African green monkeysDopamine concentrationsMale African green monkeysFetal dopamine neuronsSystemic MPTP administrationIdiopathic Parkinson's diseaseStriatum of MPTPSham-operated monkeysPostmortem brain tissueAfrican green monkeysMore variable effectsNeuronal synaptic connectionsHost neuronsHost striatumHost brainMPTP administrationGestational ageSubstantia nigraNeuronal effects
1994
Peripheral nerve-dopamine neuron co-grafts in mptp-treated monkeys: Augmentation of tyrosine hydroxylase-positive fiber staining and dopamine content in host systems
Collier T, Elsworth J, Taylor J, Sladek J, Roth R, Redmond D. Peripheral nerve-dopamine neuron co-grafts in mptp-treated monkeys: Augmentation of tyrosine hydroxylase-positive fiber staining and dopamine content in host systems. Neuroscience 1994, 61: 875-889. PMID: 7838385, DOI: 10.1016/0306-4522(94)90410-3.Peer-Reviewed Original ResearchConceptsDopamine neuronsCaudate nucleusNon-human primatesLateral ventricleSeptal areaDopamine systemEmbryonic ventral mesencephalic tissueTyrosine hydroxylase-positive fibersHomovanillic acid/dopamine ratioDopamine neuron graftsDopamine-depleted monkeysEmbryonic ventral mesencephalonGrafted dopamine neuronsVentral mesencephalic tissueLateral septal areaLevels of dopamineMesencephalic dopamine neuronsMetabolite homovanillic acidBrain dopamine systemsMPTP-treated monkeysDirection of normalizationAfrican green monkeysInjury-induced regenerationMesencephalic tissueSaphenous nerve