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Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration.
Neuroscience. 2013 Oct 10; 250:715-32.N

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.

Authors+Show Affiliations

Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-970 Campinas, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23896572

Citation

Spejo, A B., et al. "Neuroprotective Effects of Mesenchymal Stem Cells On Spinal Motoneurons Following Ventral Root Axotomy: Synapse Stability and Axonal Regeneration." Neuroscience, vol. 250, 2013, pp. 715-32.
Spejo AB, Carvalho JL, Goes AM, et al. Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration. Neuroscience. 2013;250:715-32.
Spejo, A. B., Carvalho, J. L., Goes, A. M., & Oliveira, A. L. (2013). Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration. Neuroscience, 250, 715-32. https://doi.org/10.1016/j.neuroscience.2013.07.043
Spejo AB, et al. Neuroprotective Effects of Mesenchymal Stem Cells On Spinal Motoneurons Following Ventral Root Axotomy: Synapse Stability and Axonal Regeneration. Neuroscience. 2013 Oct 10;250:715-32. PubMed PMID: 23896572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration. AU - Spejo,A B, AU - Carvalho,J L, AU - Goes,A M, AU - Oliveira,A L R, Y1 - 2013/07/27/ PY - 2013/02/02/received PY - 2013/07/18/revised PY - 2013/07/18/accepted PY - 2013/7/31/entrez PY - 2013/7/31/pubmed PY - 2014/4/5/medline KW - BDNF KW - CL KW - DMEM KW - Dulbeco’s modified eagle medium KW - EGFP KW - IL KW - MSC KW - PB KW - PBS KW - PNS KW - VRA KW - VRC KW - brain-derived neurotrophic factor KW - contralateral side to lesion KW - enhanced green fluorescent protein KW - functional recovery KW - ipsilateral side to lesion KW - mesenchymal stem cells KW - peripheral nervous system KW - phosphate buffer KW - phosphate-buffered saline KW - regeneration KW - stem cells KW - synaptic plasticity KW - ventral root avulsion KW - ventral root crushing SP - 715 EP - 32 JF - Neuroscience JO - Neuroscience VL - 250 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/23896572/Neuroprotective_effects_of_mesenchymal_stem_cells_on_spinal_motoneurons_following_ventral_root_axotomy:_synapse_stability_and_axonal_regeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00625-8 DB - PRIME DP - Unbound Medicine ER -