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Blockade of ATP P2X7 receptor enhances ischiatic nerve regeneration in mice following a crush injury.
Brain Res 2017; 1669:69-78BR

Abstract

Preventing damage caused by nerve degeneration is a great challenge. There is a growing body of evidence implicating extracellular nucleotides and their P2 receptors in many pathophysiological mechanisms. In this work we aimed to investigate the effects of the administration of Brilliant Blue G (BBG) and Pyridoxalphosphate-6-azophenyl-2', 4'- disulphonic acid (PPADS), P2X7 and P2 non-selective receptor antagonists, respectively, on sciatic nerve regeneration. Four groups of mice that underwent nerve crush lesion were used: two control groups treated with vehicle (saline), a group treated with BBG and a group treated with PPADS during 28days. Gastrocnemius muscle weight was evaluated. For functional evaluation we used the Sciatic Functional Index (SFI) and the horizontal ladder walking test. Nerves, dorsal root ganglia and spinal cords were processed for light and electron microscopy. Antinoceptive effects of BBG and PPADS were evaluated through von Frey E, and the levels of IL-1β and TNF-α were analyzed by ELISA. BBG promoted an increase in the number of myelinated fibers and on axon, fiber and myelin areas. BBG and PPADS led to an increase of TNF-α and IL-1β in the nerve on day 1 and PPADS caused a decrease of IL-1β on day 7. Mechanical allodynia was reversed on day 7 in the groups treated with BBG and PPADS. We concluded that BBG promoted a better morphological regeneration after ischiatic crush injury, but this was not followed by anticipation of functional improvement. In addition, both PPADS and BBG presented anti-inflammatory as well as antinociceptive effects.

Authors+Show Affiliations

Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.Laboratório de Farmacologia das Toxinas, Programa de Pós-Graduação em Farmacologia e Química Medicinal, ICB, CCS, UFRJ, Brazil.Laboratório de Farmacologia das Toxinas, Programa de Pós-Graduação em Farmacologia e Química Medicinal, ICB, CCS, UFRJ, Brazil.Laboratório de Regeneração Neural e Função, Departamento de Neurobiologia, Instituto de Biologia, UFF, Rio de Janeiro, Brazil.Laboratório de Neurociências e Comportamento, Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, UFC, Ceará, Brazil. Electronic address: gmatos@ufc.br.Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil. Electronic address: anamartinez@hucff.ufrj.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28554806

Citation

Ribeiro, Tatianne, et al. "Blockade of ATP P2X7 Receptor Enhances Ischiatic Nerve Regeneration in Mice Following a Crush Injury." Brain Research, vol. 1669, 2017, pp. 69-78.
Ribeiro T, Oliveira JT, Almeida FM, et al. Blockade of ATP P2X7 receptor enhances ischiatic nerve regeneration in mice following a crush injury. Brain Res. 2017;1669:69-78.
Ribeiro, T., Oliveira, J. T., Almeida, F. M., Tomaz, M. A., Melo, P. A., Marques, S. A., ... Martinez, A. M. B. (2017). Blockade of ATP P2X7 receptor enhances ischiatic nerve regeneration in mice following a crush injury. Brain Research, 1669, pp. 69-78. doi:10.1016/j.brainres.2017.05.025.
Ribeiro T, et al. Blockade of ATP P2X7 Receptor Enhances Ischiatic Nerve Regeneration in Mice Following a Crush Injury. Brain Res. 2017 Aug 15;1669:69-78. PubMed PMID: 28554806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of ATP P2X7 receptor enhances ischiatic nerve regeneration in mice following a crush injury. AU - Ribeiro,Tatianne, AU - Oliveira,Júlia Teixeira, AU - Almeida,Fernanda Martins, AU - Tomaz,Marcelo Amorim, AU - Melo,Paulo A, AU - Marques,Suelen Adriani, AU - de Andrade,Geanne Matos, AU - Martinez,Ana Maria Blanco, Y1 - 2017/05/26/ PY - 2016/09/15/received PY - 2017/05/15/revised PY - 2017/05/22/accepted PY - 2017/5/31/pubmed PY - 2018/4/13/medline PY - 2017/5/31/entrez KW - BBG KW - Ischiatic nerve KW - Mice KW - P2 receptor antagonists and crush injury KW - PPADS SP - 69 EP - 78 JF - Brain research JO - Brain Res. VL - 1669 N2 - Preventing damage caused by nerve degeneration is a great challenge. There is a growing body of evidence implicating extracellular nucleotides and their P2 receptors in many pathophysiological mechanisms. In this work we aimed to investigate the effects of the administration of Brilliant Blue G (BBG) and Pyridoxalphosphate-6-azophenyl-2', 4'- disulphonic acid (PPADS), P2X7 and P2 non-selective receptor antagonists, respectively, on sciatic nerve regeneration. Four groups of mice that underwent nerve crush lesion were used: two control groups treated with vehicle (saline), a group treated with BBG and a group treated with PPADS during 28days. Gastrocnemius muscle weight was evaluated. For functional evaluation we used the Sciatic Functional Index (SFI) and the horizontal ladder walking test. Nerves, dorsal root ganglia and spinal cords were processed for light and electron microscopy. Antinoceptive effects of BBG and PPADS were evaluated through von Frey E, and the levels of IL-1β and TNF-α were analyzed by ELISA. BBG promoted an increase in the number of myelinated fibers and on axon, fiber and myelin areas. BBG and PPADS led to an increase of TNF-α and IL-1β in the nerve on day 1 and PPADS caused a decrease of IL-1β on day 7. Mechanical allodynia was reversed on day 7 in the groups treated with BBG and PPADS. We concluded that BBG promoted a better morphological regeneration after ischiatic crush injury, but this was not followed by anticipation of functional improvement. In addition, both PPADS and BBG presented anti-inflammatory as well as antinociceptive effects. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/28554806/Blockade_of_ATP_P2X7_receptor_enhances_ischiatic_nerve_regeneration_in_mice_following_a_crush_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(17)30221-4 DB - PRIME DP - Unbound Medicine ER -