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Type: Artigo de periódico
Title: Neuroprotective Effects Of Mesenchymal Stem Cells On Spinal Motoneurons Following Ventral Root Axotomy: Synapse Stability And Axonal Regeneration.
Author: Spejo, A B
Carvalho, J L
Goes, A M
Oliveira, A L R
Abstract: Compression of spinal roots is an important medical problem, which may arise from intervertebral disc herniation, tumor growth or as a result of high energy accidents. Differently from avulsion, root crushing maintains the central/peripheral nervous system (CNS/PNS) connection, although the axons are axotomized and motoneurons degenerate. Such neuronal death may decrease and delay motor function recovery. In the present study we have investigated the neuroprotective effects of mesenchymal stem cell (MSC) therapy following such proximal lesions. Motor recovery and synaptic stabilization were analyzed by the use of morphological and functional approaches. For that, crushing the ventral roots at L4, L5 and L6 was unilaterally performed in Lewis rats. Four weeks after injury, an increased motoneuron survival was observed in the MSC-treated group, coupled with a smaller decrease of inputs at the motoneuron surface and nearby neuropil, seen by synaptophysin and synapsin immunolabeling and decreased astrogliosis, seen by GFAP immunolabeling. In this sense, MSC-treated group displayed a significant preservation of GABAergic terminals, indicating a possible neuroprotection to glutamate excitotoxicity. Motor function recovery was acutely improved in MSC-treated group as compared to Dulbeco's modified eagle medium (DMEM)-treated. Overall, we provide evidence that ventral root crushing (VRC), although milder than avulsion, results in significant loss of motoneurons (~51%) that can be reduced by MSC administration within the spinal cord. Such treatment also improves the number of synapses immunoreactive against molecules present in inhibitory inputs. Also, an increased number of regenerated axons was obtained in the MSC-treated group, in comparison to the DMEM-treated control. Overall, MSC therapy acutely improved limb strength and gait coordination, indicating a possible clinical application of such treatment following proximal lesions at the CNS/PNS interface.
Subject: Animals
Cell Survival
Cells, Cultured
Flow Cytometry
Mesenchymal Stem Cell Transplantation
Motor Neurons
Muscle Strength
Nerve Crush
Nerve Regeneration
Rats, Inbred Lew
Recovery Of Function
Sciatic Nerve
Spinal Cord
Spinal Nerve Roots
Dulbeco’s Modified Eagle Medium
Brain-derived Neurotrophic Factor
Contralateral Side To Lesion
Enhanced Green Fluorescent Protein
Functional Recovery
Ipsilateral Side To Lesion
Mesenchymal Stem Cells
Peripheral Nervous System
Phosphate Buffer
Phosphate-buffered Saline
Stem Cells
Synaptic Plasticity
Ventral Root Avulsion
Ventral Root Crushing
Citation: Neuroscience. v. 250, p. 715-32, 2013-Oct.
Rights: fechado
Identifier DOI: 10.1016/j.neuroscience.2013.07.043
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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