title: Influence of delivery method on neuroprotection by bone marrow mononuclear cell therapy following ventral root reimplantation with fibrin sealant.
abstract: The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results.
authors.affiliation: Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Barbizan
authors.affiliation: Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Mateus V
authors.initials: MV
authors.lastname: Castro
authors.affiliation: Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, São Paulo, Brazil.
authors.forename: Benedito
authors.initials: B
authors.lastname: Barraviera
authors.affiliation: Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, São Paulo, Brazil.
authors.forename: Rui S
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Alexandre L R
authors.initials: AL
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D020209:Cranial Nerve Injuries; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use*; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D017628:Microglia / Q000502:physiology; D009417:Nerve Tissue / Q000637:transplantation; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D013126:Spinal Nerve Roots / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015718:Fibrin Tissue Adhesive; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein