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Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL).
J Neurosci Res. 2019 04; 97(4):520-534.JN

Abstract

Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12 mg/kg, n = 5), and (c) VRC-TEMPOL treatment (250 mg/kg, n = 5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning.

Authors+Show Affiliations

Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.

Pub Type(s)

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

Language

eng

PubMed ID

30549080

Citation

Spejo, Aline Barroso, et al. "Synapse Preservation and Decreased Glial Reactions Following Ventral Root Crush (VRC) and Treatment With 4-hydroxy-tempo (TEMPOL)." Journal of Neuroscience Research, vol. 97, no. 4, 2019, pp. 520-534.
Spejo AB, Teles CB, Zuccoli GDS, et al. Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL). J Neurosci Res. 2019;97(4):520-534.
Spejo, A. B., Teles, C. B., Zuccoli, G. D. S., & Oliveira, A. L. R. (2019). Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL). Journal of Neuroscience Research, 97(4), 520-534. https://doi.org/10.1002/jnr.24365
Spejo AB, et al. Synapse Preservation and Decreased Glial Reactions Following Ventral Root Crush (VRC) and Treatment With 4-hydroxy-tempo (TEMPOL). J Neurosci Res. 2019;97(4):520-534. PubMed PMID: 30549080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL). AU - Spejo,Aline Barroso, AU - Teles,Caroline Brandão, AU - Zuccoli,Giuliana da Silva, AU - Oliveira,Alexandre Leite Rodrigues de, Y1 - 2018/12/14/ PY - 2018/07/24/received PY - 2018/11/20/revised PY - 2018/11/20/accepted PY - 2018/12/15/pubmed PY - 2020/7/17/medline PY - 2018/12/15/entrez KW - TEMPOL KW - gliosis KW - inflammation KW - motoneuron KW - spinal cord KW - ventral root lesion SP - 520 EP - 534 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 97 IS - 4 N2 - Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12 mg/kg, n = 5), and (c) VRC-TEMPOL treatment (250 mg/kg, n = 5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/30549080/Synapse_preservation_and_decreased_glial_reactions_following_ventral_root_crush_(VRC)_and_treatment_with_4-hydroxy-tempo_(TEMPOL) DB - PRIME DP - Unbound Medicine ER -