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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Glial cell line-derived neurotrophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth

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Autor(es):
Guzen, Fausto Pierdona [1] ; de Almeida Leme, Ricardo Jose [1] ; Ramos de Andrade, Michele Schultz [1] ; de Luca, Bianca Aparecida [1] ; Chadi, Gerson [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Neurol, Sch Med, Neuroregenerat Ctr, BR-01246903 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: RESTORATIVE NEUROLOGY AND NEUROSCIENCE; v. 27, n. 1, p. 1-16, 2009.
Citações Web of Science: 21
Resumo

Purpose: The aversive nature of regenerative milieu is the main problem related to the failure of neuronal restoration in the injured spinal cord which however might be addressed with an adequate repair intervention. We evaluated whether glial cell line-derived neurotrophic factor (GDNF) may increase the ability of sciatic nerve graft, placed in a gap promoted by complete transections of the spinal cord, to enhance motor recovery and local fiber growth. Methods: Rats received a 4 mm-long gap at low thoracic level and were repaired with a fragment of the sciatic nerve. GDNF was added (NERVE+GDNF) or not to the grafts (NERVE-GDNF). Motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively, and also the spontaneous motor behavior in an open field by means of an infrared motion sensor activity monitor were analyzed. At the end of the third month post surgery, the tissue composed by the graft and the adjacent regions of the spinal cord was removed and submitted to the immunohistochemistry of the neurofilament-200 (NF-200), growth associated protein-43 (GAP-43), microtubule associated protein-2 (MAP-2), 5-hidroxytryptamine (serotonin, 5-HT) and calcitonin gene related peptide (CGRP). The immunoreactive fibers were quantified at the epicenter of the graft by means of stereological procedures. Results: Higher BBB and lower CBS levels (p < 0.001) were found in NERVE+GDNF rats. GDNF added to the graft increased the levels of individual sensorimotor tests mainly at the third month. Analysis of the spontaneous motor behavior showed decreases in the time and number of small movement events by the third month without changes in time and number of large movement events in the NERVE+GDNF rats. Immunoreactive fibers were encountered inside the grafts and higher amounts of NF-200, GAP-43 and MAP-2 fibers were found in the epicenter of the graft when GDNF was added. A small amount of descending 5-HT fibers was seen reentering in the adjacent caudal levels of the spinal cords which were grafted in the presence of GDNF, event that has not occurred without the neurotrophic factor. GDNF in the graft also led to a large amount of MAP-2 perikarya and fibers in the caudal levels of the cord gray matter, as determined by the microdensitometric image analysis. Conclusions: GDNF added to the nerve graft favored the motor recovery, local neuronal fiber growth and neuroplasticity in the adjacent spinal cord. (AU)

Processo FAPESP: 99/01319-1 - Análise da regeneração da medula espinhal após enxertos de nervos ou inoculação de células de Schwann em presença do fator neurotrófico derivado de células gliais (GDNF)
Beneficiário:Gerson Chadi
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 98/13122-5 - Efeito da ativação neuronal pela atividade física nas respostas tróficas e plásticas neuronais e gliais do sistema nervoso central lesado ou não de ratos: estudo imunohistoquímico combinado às análises estereológica e microdensitométrica quantitativas
Beneficiário:Gerson Chadi
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/00491-3 - Análise do potencial das células de Schwann cultivadas e tratadas com o PEDF favorecem o trofismo de neurônios medulares in vitro a induzirem a regeneração e a recuperação motora de ratos submetidos ao trauma contuso da medula espinal pelo Impactor
Beneficiário:Gerson Chadi
Modalidade de apoio: Auxílio à Pesquisa - Regular