PMID- 29713994
OWN - NLM
STAT- MEDLINE
DCOM- 20181106
LR  - 20191210
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 34
IP  - 3
DP  - 2018 Oct
TI  - Dimethyl Fumarate Limits Neuroinflammation and Oxidative Stress and Improves 
      Cognitive Impairment After Polymicrobial Sepsis.
PG  - 418-430
LID - 10.1007/s12640-018-9900-8 [doi]
AB  - Sepsis is caused by a dysregulated host response to infection, often associated 
      with acute central nervous system (CNS) dysfunction, which results in long-term 
      cognitive impairment. Dimethyl fumarate (DMF) is an important agent against 
      inflammatory response and reactive species in CNS disorders. Evaluate the effect 
      of DMF on acute and long-term brain dysfunction after experimental sepsis in 
      rats. Male Wistar rats were submitted to the cecal ligation and puncture (CLP) 
      model. The groups were divided into sham (control) + vehicle, sham + NAC, sham + 
      DMF, CLP + vehicle, CLP + NAC, and CLP + DMF. The animals were treated with DMF 
      (15 mg/kg at 0 and 12 h after CLP, per gavage) and the administration of 
      n-acetylcysteine (NAC) (20 mg/kg; 3, 6, and 12 h after CLP, subcutaneously) was 
      used as positive control. Twenty-four hours after CLP, cytokines, myeloperoxidase 
      (MPO), nitrite/nitrate (N/N), oxidative damage to lipids and proteins, and 
      antioxidant enzymes were evaluated in the hippocampus, total cortex, and 
      prefrontal cortex. At 10 days after sepsis induction, behavioral tests were 
      performed to assess cognitive damage. We observed an increase in cytokine levels, 
      MPO activity, N/N concentration, and oxidative damage, a reduction in SOD and GPx 
      activity in the brain structures, and cognitive damage in CLP rats. DMF treatment 
      was effective in reversing these parameters. DMF reduces sepsis-induced 
      neuroinflammation, oxidative stress, and cognitive impairment in rats subjected 
      to the CLP model.
FAU - Zarbato, Graciela Freitas
AU  - Zarbato GF
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - de Souza Goldim, Mariana Pereira
AU  - de Souza Goldim MP
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Giustina, Amanda Della
AU  - Giustina AD
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Danielski, Lucineia Gainski
AU  - Danielski LG
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Mathias, Khiany
AU  - Mathias K
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Florentino, Drielly
AU  - Florentino D
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - de Oliveira Junior, Aloir Neri
AU  - de Oliveira Junior AN
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - da Rosa, Naiana
AU  - da Rosa N
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Laurentino, Ana Olivia
AU  - Laurentino AO
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Trombetta, Taina
AU  - Trombetta T
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Gomes, Maria Luiza
AU  - Gomes ML
AD  - Laboratory Inborn Errors of Metabolism, Graduate Program in Health Sciences, 
      Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciuma, 
      SC, Brazil.
FAU - Steckert, Amanda Valnier
AU  - Steckert AV
AD  - Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences 
      Unit, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil.
FAU - Moreira, Ana Paula
AU  - Moreira AP
AD  - Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences 
      Unit, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil.
FAU - Schuck, Patricia Fernanda
AU  - Schuck PF
AD  - Laboratory Inborn Errors of Metabolism, Graduate Program in Health Sciences, 
      Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciuma, 
      SC, Brazil.
FAU - Fortunato, Jucelia Jeremias
AU  - Fortunato JJ
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil.
FAU - Barichello, Tatiana
AU  - Barichello T
AD  - Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences 
      Unit, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil.
AD  - Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth), Houston, TX, 
      USA.
FAU - Petronilho, Fabricia
AU  - Petronilho F
AD  - Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate 
      Program in Health Sciences, Health Sciences Unit, University of South Santa 
      Catarina, Tubarao, SC, Brazil. fabricia.petronilho@unisul.br.
LA  - eng
PT  - Journal Article
DEP - 20180430
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - FO2303MNI2 (Dimethyl Fumarate)
SB  - IM
MH  - Animals
MH  - Catalase/metabolism
MH  - *Cognition Disorders/complications/etiology/therapy
MH  - Cytokines/metabolism
MH  - Dimethyl Fumarate/*therapeutic use
MH  - Disease Models, Animal
MH  - Exploratory Behavior/drug effects
MH  - Glutathione Peroxidase/metabolism
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Inflammation/*drug therapy/*etiology
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Neutrophil Infiltration/drug effects
MH  - Nitrates/metabolism
MH  - Nitrites/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Protein Carbonylation/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Recognition, Psychology/drug effects
MH  - Sepsis/*complications
MH  - Superoxide Dismutase/metabolism
OTO - NOTNLM
OT  - Cognitive impairment
OT  - Dimethyl fumarate
OT  - Neuroinflammation
OT  - Oxidative stress
OT  - Sepsis
EDAT- 2018/05/02 06:00
MHDA- 2018/11/07 06:00
CRDT- 2018/05/02 06:00
PHST- 2017/10/23 00:00 [received]
PHST- 2018/04/06 00:00 [accepted]
PHST- 2018/04/02 00:00 [revised]
PHST- 2018/05/02 06:00 [pubmed]
PHST- 2018/11/07 06:00 [medline]
PHST- 2018/05/02 06:00 [entrez]
AID - 10.1007/s12640-018-9900-8 [pii]
AID - 10.1007/s12640-018-9900-8 [doi]
PST - ppublish
SO  - Neurotox Res. 2018 Oct;34(3):418-430. doi: 10.1007/s12640-018-9900-8. Epub 2018 
      Apr 30.