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Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats.
Brain Res Bull. 2014 Jul; 106:1-8.BR

Abstract

Peripheral nerve injury in newborn rats triggers extensive neuronal death within the spinal cord. Because most neurodegeneration is related to oxidative stress and apoptosis, the use of antioxidants may be of therapeutic interest. Tempol is promising because of its ability to chelate reactive oxygen species and to minimize or even prevent tissue damage. Here, we evaluated neuroprotective effects of tempol following neonatal sciatic nerve transection. Two-day-old pups underwent sciatic nerve axotomy followed by tempol (12, 24 and 48 mg/kg) treatment (i.p.) at 10 min, 6 h, and every 24 h up to 1 week after injury. The rats were then killed for lumbar intumescence analysis. Nissl staining, TUNEL, synaptophysin immunolabeling and qRT-PCR (Caspase 3, Bax and Bcl2) were carried out. The results indicated that tempol treatment, at 24 mg/kg, increased up to 21% spinal cord motoneuron survival (p<0.001), also preserving pre-synaptic terminals in the neuropile. Likewise, the TUNEL-positive cell number decreased in tempol-treated animals. qRT-PCR results indicated differential increase in Caspase 3 (3-fold), Bax (13-fold) and Bcl2 (28-fold) gene expression, after 12 h following axotomy and tempol treatment. In conclusion, tempol administration has proven to be neuroprotective after neonatal nerve injury, leading to improved motoneuron survival, synapse preservation and minimizing apoptosis.

Authors+Show Affiliations

Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-907 Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-907 Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-907 Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-907 Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), CP 6109, CEP 13083-907 Campinas, SP, Brazil. Electronic address: alroliv@unicamp.br.

Pub Type(s)

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

Language

eng

PubMed ID

24769526

Citation

Chiarotto, Gabriela Bortolança, et al. "Neuroprotective Effect of Tempol (4 Hydroxy-tempo) On Neuronal Death Induced By Sciatic Nerve Transection in Neonatal Rats." Brain Research Bulletin, vol. 106, 2014, pp. 1-8.
Chiarotto GB, Drummond L, Cavarretto G, et al. Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats. Brain Res Bull. 2014;106:1-8.
Chiarotto, G. B., Drummond, L., Cavarretto, G., Bombeiro, A. L., & de Oliveira, A. L. (2014). Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats. Brain Research Bulletin, 106, 1-8. https://doi.org/10.1016/j.brainresbull.2014.04.010
Chiarotto GB, et al. Neuroprotective Effect of Tempol (4 Hydroxy-tempo) On Neuronal Death Induced By Sciatic Nerve Transection in Neonatal Rats. Brain Res Bull. 2014;106:1-8. PubMed PMID: 24769526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats. AU - Chiarotto,Gabriela Bortolança, AU - Drummond,Luisa, AU - Cavarretto,Gabriela, AU - Bombeiro,André Luis, AU - de Oliveira,Alexandre Leite Rodrigues, Y1 - 2014/04/25/ PY - 2013/11/21/received PY - 2014/04/01/revised PY - 2014/04/17/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2015/3/13/medline KW - Apoptosis KW - Neuronal survival KW - Neuroprotection KW - Sciatic nerve KW - Spinal cord KW - Tempol SP - 1 EP - 8 JF - Brain research bulletin JO - Brain Res. Bull. VL - 106 N2 - Peripheral nerve injury in newborn rats triggers extensive neuronal death within the spinal cord. Because most neurodegeneration is related to oxidative stress and apoptosis, the use of antioxidants may be of therapeutic interest. Tempol is promising because of its ability to chelate reactive oxygen species and to minimize or even prevent tissue damage. Here, we evaluated neuroprotective effects of tempol following neonatal sciatic nerve transection. Two-day-old pups underwent sciatic nerve axotomy followed by tempol (12, 24 and 48 mg/kg) treatment (i.p.) at 10 min, 6 h, and every 24 h up to 1 week after injury. The rats were then killed for lumbar intumescence analysis. Nissl staining, TUNEL, synaptophysin immunolabeling and qRT-PCR (Caspase 3, Bax and Bcl2) were carried out. The results indicated that tempol treatment, at 24 mg/kg, increased up to 21% spinal cord motoneuron survival (p<0.001), also preserving pre-synaptic terminals in the neuropile. Likewise, the TUNEL-positive cell number decreased in tempol-treated animals. qRT-PCR results indicated differential increase in Caspase 3 (3-fold), Bax (13-fold) and Bcl2 (28-fold) gene expression, after 12 h following axotomy and tempol treatment. In conclusion, tempol administration has proven to be neuroprotective after neonatal nerve injury, leading to improved motoneuron survival, synapse preservation and minimizing apoptosis. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/24769526/Neuroprotective_effect_of_tempol__4_hydroxy_tempo__on_neuronal_death_induced_by_sciatic_nerve_transection_in_neonatal_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(14)00064-1 DB - PRIME DP - Unbound Medicine ER -