Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL)

Autor(es)

Spejo, Aline Barroso ^[1] ; Teles, Caroline Brandao ^[1] ; Zuccoli, Giuliana da Silva ^[1] ; Rodrigues de Oliveira, Alexandre Leite ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Neuroscience Research; v. 97, n. 4, p. 520-534, APR 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 14/12707-4 - Efeito neuroprotetor do tempol (4-hidroxi tempo) após axôniotmese de raízes motoras na interface do SNC e SNP
• Beneficiário: Giuliana da Silva Zuccoli
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/22750-9 - Emprego de selante de fibrina combinado com células tronco mesenquimais para o reparo de lesão no funículo anterior: efeitos sobre a inflamação, neuroproteção e regeneração axonal.
• Beneficiário: Aline Barroso Spejo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/12671-0 - Efeitos do tempol (4-hidroxi-tempo) sobre a plasticidade sináptica, inflamação e regeneração após esmagamento de raízes ventrais na interface do SNC e SNP
• Beneficiário: Caroline Brandão Teles Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/06892-3 - Utilização de células tronco mesenquimais na interface do sistema nervoso central e periférico: reparo de lesões proximais
• Beneficiário: Alexandre Leite Rodrigues de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático