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Morphological Changes in a Severe Model of Parkinson’s Disease and Its Suitability to Test the Therapeutic Effects of Microencapsulated Neurotrophic Factors

dc.contributor.authorRequejo C.
dc.contributor.authorRuiz-Ortega J.A.
dc.contributor.authorBengoetxea H.
dc.contributor.authorGarcía-Blanco A.
dc.contributor.authorHerrán E.
dc.contributor.authorAristieta A.
dc.contributor.authorIgartua M.
dc.contributor.authorPedraz J.L.
dc.contributor.authorUgedo L.
dc.contributor.authorHernández R.M.
dc.contributor.authorLafuente J.V.
dc.date.accessioned2020-09-02T22:26:54Z
dc.date.available2020-09-02T22:26:54Z
dc.date.issued2017
dc.identifier10.1007/s12035-016-0244-1
dc.identifier.citation54, 10, 7722-7735
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5974
dc.descriptionThe unilateral 6-hydroxydopamine (6-OHDA) lesion of medial forebrain bundle (MFB) in rats affords us to study the advanced stages of Parkinson’s disease (PD). Numerous evidences suggest synergic effects when various neurotrophic factors are administered in experimental models of PD. The aim of the present work was to assess the morphological changes along the rostro-caudal axis of caudo-putamen complex and substantia nigra (SN) in the referred model in order to test the suitability of a severe model to evaluate new neurorestorative therapies. Administration of 6-OHDA into MFB in addition to a remarkable depletion of dopamine in the nigrostriatal system induced an increase of glial fibrillary acidic protein (GFAP)-positive cells in SN and an intense immunoreactivity for OX-42, vascular endothelial growth factor (VEGF), and Lycopersycum esculentum agglutinin (LEA) in striatum and SN. Tyrosine hydroxylase (TH) immunostaining revealed a significant decrease of the TH-immunopositive striatal volume in 6-OHDA group from rostral to caudal one. The loss of TH-immunoreactive (TH-ir) neurons and axodendritic network (ADN) was higher in caudal sections. Morphological recovery after the implantation of microspheres loaded with VEGF and glial cell line-derived neurotrophic factor (GDNF) in parkinsonized rats was related to the preservation of the TH-ir cell number and ADN in the caudal region of the SN. In addition, these findings support the neurorestorative role of VEGF+GDNF in the dopaminergic system and the synergistic effect between both factors. On the other hand, a topological distribution of the dopaminergic system was noticeable in the severe model, showing a selective vulnerability to 6-OHDA and recovering after treatment. © 2016, Springer Science+Business Media New York.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subject6-OHDA
dc.subjectGDNF
dc.subjectNeuroregeneration
dc.subjectParkinson’s disease
dc.subjectRostro-caudal gradient
dc.subjectVEGF
dc.subjectdesipramine
dc.subjectdopamine
dc.subjectglial cell line derived neurotrophic factor
dc.subjectglial fibrillary acidic protein
dc.subjectmicrosphere
dc.subjectoxidopamine
dc.subjectpargyline
dc.subjecttyrosine 3 monooxygenase
dc.subjectvasculotropin
dc.subjectglial cell line derived neurotrophic factor
dc.subjectneuroprotective agent
dc.subjectvascular endothelial growth factor A, rat
dc.subjectvasculotropin A
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbrain nerve cell
dc.subjectcaudate nucleus
dc.subjectcell count
dc.subjectcontrolled study
dc.subjectcorpus striatum
dc.subjectdisease severity
dc.subjectdopaminergic system
dc.subjectfemale
dc.subjecthistopathology
dc.subjectimmunoreactivity
dc.subjectmedial forebrain bundle
dc.subjectmicroencapsulation
dc.subjectnigroneostriatal system
dc.subjectnonhuman
dc.subjectParkinson disease
dc.subjectpathogenesis
dc.subjectprotein function
dc.subjectputamen
dc.subjectrat
dc.subjectsubstantia nigra
dc.subjectanimal
dc.subjectdrug formulation
dc.subjectparkinsonism
dc.subjectpathology
dc.subjectprocedures
dc.subjectseverity of illness index
dc.subjectSprague Dawley rat
dc.subjecttreatment outcome
dc.subjectAnimals
dc.subjectDrug Compounding
dc.subjectFemale
dc.subjectGlial Cell Line-Derived Neurotrophic Factor
dc.subjectNeuroprotective Agents
dc.subjectParkinsonian Disorders
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectSeverity of Illness Index
dc.subjectTreatment Outcome
dc.subjectVascular Endothelial Growth Factor A
dc.titleMorphological Changes in a Severe Model of Parkinson’s Disease and Its Suitability to Test the Therapeutic Effects of Microencapsulated Neurotrophic Factors
dc.typeArticle


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