Efeito neuroprotetor do JM-20 em ratos submetidos a traumatismo cranioencefálico leve

• Ano de defesa: 2021
• Autor(a) principal: Furtado, Andrezza Bond Vieira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/26339/0013000014ftb
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Bioquímica; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Neuroproteção; Neurodegeneração; Droga multi-alvo; Neuroinflamação; Disfunção mitocondrial; Sobrevivência neuronal; Neuroprotection; Neurodegeneration; Multi-target drug; Neuroinflammation; Mitochondrial dysfunction; Neuronal survival; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/24412

Traumatic brain injury (TBI) is a multisystemic pathology with interactions between central nervous system, peripheral nervous system and immune system. It is one of the main causes of death and desability worldwide. The pathophysiology of TBI involves cell death pathways and tissue loss that lead to neurodegeneration and deficits in neurological function. It is estimated that 75 to 90% of TBI cases are classified as mild, and the damage following TBI may be underestimated. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects on TBI outcomes of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido[2,3-b][1,5]benzodiazepine (JM-20). JM-20 emerge as a neuroprotective drug because it targets mediators involved in cell death events: calcium channels, due to the dihydropyridine portion; and GABAa receptors, due to benzodiazepine action. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). 24 h following TBI, JM-20 treatment was able to attenuate locomotor and short-term memory deficits; decrease brain edema; avoid the exacerbated activation of glial cells and consequently the pro-inflammatory signaling by decreasing release of pro-inflammatory cytokines and higher release of neurotrophins; avoid mitochondrial dysfunction through increased oxygen flux consumption in oxidative phosphorylation, and then, improve mitochondrial functionality; JM-20 treatment was also able to mantain the activation of an important pathway related to cellular cascades. Based on these, is possible to confirm that JM-20 has neuroprotective effects by modulating important secondary injury targets and corroborate our hypothesis that JM-20 may become a promising treatment strategy to TBI.