Lipoic Acid and Fish Oil Combination Potentiates Neuroinflammation and Oxidative Stress Regulation and Prevents Cognitive Decline of Rats After Sepsis

Molecular Neurobiology - Tập 57 - Trang 4451-4466 - 2020
Amanda Della Giustina1, Mariana Pereira de Souza Goldim1, Lucinéia Gainski Danielski1, Leandro Garbossa1, Aloir Neri Oliveira Junior1, Thainá Cidreira1, Taís Denicol1, Sandra Bonfante1, Naiana da Rosa1, Jucélia Jeremias Fortunato1, Juliete Palandi2, Bruna Hoffmann de Oliveira2, Daniel Fernandes Martins2, Franciane Bobinski2, Michelle Garcez3, Tatiani Bellettini-Santos3, Josiane Budni3, Gabriela Colpo4, Giselli Scaini4, Vijayasree V. Giridharan4, Tatiana Barichello4,5, Fabricia Petronilho1,6
1Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarão, Brazil
2Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Brazil
3Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
4Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, USA
5Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
6Laboratório de Neurobiologia de Processos Inflamatórios e Metabólicos, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Tubarão, Brazil

Tóm tắt

Sepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopolysaccharide (LPS) and FO or LA, alone or combined, for 24 h. Cytokine levels were measured. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) and treated orally with FO, LA, or FO+LA. At 24 h after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of cytokines, myeloperoxidase (MPO) activity, protein carbonyls, superoxide dismutase (SOD), and catalase (CAT) activity. At 10 days after surgery, brain-derived neurotrophic factor (BDNF) levels were determined and behavioral tests were performed. The combination diminished in vitro levels of pro-inflammatory cytokines. The combination reduced TNF-α in the cortex, IL-1β in the prefrontal cortex, as well as MPO activity, and decreased protein carbonyls formation in all structures. The combination enhanced catalase activity in the prefrontal cortex and hippocampus, elevated BDNF levels in all structures, and prevented behavioral impairment. In summary, the combination was effective in preventing cognitive damage by reducing neuroinflammation and oxidative stress and increasing BDNF levels.

Tài liệu tham khảo

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