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Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

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Author(s):
Barbizan, Roberta ; Castro, Mateus V. ; Ferreira, Rui Seabra, Jr. ; Barraviera, Benedito ; Oliveira, Alexandre L. R.
Total Authors: 5
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 15, n. 11, p. 17-pg., 2014-11-01.
Abstract

We recently proposed a new surgical approach to treat ventral root avulsion, resulting in motoneuron protection. The present work combined such a surgical approach with bone marrow mononuclear cells (MC) therapy. Therefore, MC were added to the site of reimplantation. Female Lewis rats (seven weeks old) were subjected to unilateral ventral root avulsion (VRA) at L4, L5 and L6 levels and divided into the following groups (n = 5 for each group): Avulsion, sealant reimplanted roots and sealant reimplanted roots plus MC. After four weeks and 12 weeks post-surgery, the lumbar intumescences were processed by transmission electron microscopy, to analyze synaptic inputs to the repaired a motoneurons. Also, the ipsi and contralateral sciatic nerves were processed for axon counting and morphometry. The ultrastructural results indicated a significant preservation of inhibitory pre-synaptic boutons in the groups repaired with sealant alone and associated with MC therapy. Moreover, the average number of axons was higher in treated groups when compared to avulsion only. Complementary to the fiber counting, the morphometric analysis of axonal diameter and "g" ratio demonstrated that root reimplantation improved the motor component recovery. In conclusion, the data herein demonstrate that root reimplantation at the lesion site may be considered a therapeutic approach, following proximal lesions in the interface of central nervous system (CNS) and peripheral nervous system (PNS), and that MC therapy does not further improve the regenerative recovery, up to 12 weeks post lesion. (AU)

FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
Grantee:Alexandre Leite Rodrigues de Oliveira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 09/53846-9 - Recent acquisition of preparative high-performance liquid chromatograph for the purification and isolation of serine proteinases to produce fibrin sealant
Grantee:Benedito Barraviera
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 12/08101-8 - In vivo imaging of nerve regeneration following ventral root replantation with fluo-stained fibrin sealant associated with mesenchymal stem cells
Grantee:Rui Seabra Ferreira Junior
Support Opportunities: Regular Research Grants
FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
Grantee:Suely Vilela
Support Opportunities: Research Projects - Thematic Grants