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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.author | Requejo C. | |
dc.contributor.author | Ruiz-Ortega J.A. | |
dc.contributor.author | Bengoetxea H. | |
dc.contributor.author | García-Blanco A. | |
dc.contributor.author | Herrán E. | |
dc.contributor.author | Aristieta A. | |
dc.contributor.author | Igartua M. | |
dc.contributor.author | Pedraz J.L. | |
dc.contributor.author | Ugedo L. | |
dc.contributor.author | Hernández R.M. | |
dc.contributor.author | Lafuente J.V. | |
dc.date.accessioned | 2020-09-02T22:26:54Z | |
dc.date.available | 2020-09-02T22:26:54Z | |
dc.date.issued | 2017 | |
dc.identifier | 10.1007/s12035-016-0244-1 | |
dc.identifier.citation | 54, 10, 7722-7735 | |
dc.identifier.issn | 08937648 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12728/5974 | |
dc.description | The 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.iso | en | |
dc.publisher | Humana Press Inc. | |
dc.subject | 6-OHDA | |
dc.subject | GDNF | |
dc.subject | Neuroregeneration | |
dc.subject | Parkinson’s disease | |
dc.subject | Rostro-caudal gradient | |
dc.subject | VEGF | |
dc.subject | desipramine | |
dc.subject | dopamine | |
dc.subject | glial cell line derived neurotrophic factor | |
dc.subject | glial fibrillary acidic protein | |
dc.subject | microsphere | |
dc.subject | oxidopamine | |
dc.subject | pargyline | |
dc.subject | tyrosine 3 monooxygenase | |
dc.subject | vasculotropin | |
dc.subject | glial cell line derived neurotrophic factor | |
dc.subject | neuroprotective agent | |
dc.subject | vascular endothelial growth factor A, rat | |
dc.subject | vasculotropin A | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | brain nerve cell | |
dc.subject | caudate nucleus | |
dc.subject | cell count | |
dc.subject | controlled study | |
dc.subject | corpus striatum | |
dc.subject | disease severity | |
dc.subject | dopaminergic system | |
dc.subject | female | |
dc.subject | histopathology | |
dc.subject | immunoreactivity | |
dc.subject | medial forebrain bundle | |
dc.subject | microencapsulation | |
dc.subject | nigroneostriatal system | |
dc.subject | nonhuman | |
dc.subject | Parkinson disease | |
dc.subject | pathogenesis | |
dc.subject | protein function | |
dc.subject | putamen | |
dc.subject | rat | |
dc.subject | substantia nigra | |
dc.subject | animal | |
dc.subject | drug formulation | |
dc.subject | parkinsonism | |
dc.subject | pathology | |
dc.subject | procedures | |
dc.subject | severity of illness index | |
dc.subject | Sprague Dawley rat | |
dc.subject | treatment outcome | |
dc.subject | Animals | |
dc.subject | Drug Compounding | |
dc.subject | Female | |
dc.subject | Glial Cell Line-Derived Neurotrophic Factor | |
dc.subject | Neuroprotective Agents | |
dc.subject | Parkinsonian Disorders | |
dc.subject | Rats | |
dc.subject | Rats, Sprague-Dawley | |
dc.subject | Severity of Illness Index | |
dc.subject | Treatment Outcome | |
dc.subject | Vascular Endothelial Growth Factor A | |
dc.title | Morphological Changes in a Severe Model of Parkinson’s Disease and Its Suitability to Test the Therapeutic Effects of Microencapsulated Neurotrophic Factors | |
dc.type | Article |