Indole-3-guanylhydrazone hydrochloride mitigates long-term cognitive impairment in a neonatal sepsis model with involvement of MAPK and NFκB pathways.
Neurochem Int
; 134: 104647, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31877349
ABSTRACT
BACKGROUND:
Neonatal sepsis is defined as a systemic inflammatory response caused by a suspected or proven infection, occurring in the first month of life, and remains one of the main causes of morbidity and mortality in newborn and preterm infants. Frequently, survivors of neonatal sepsis have serious long-term cognitive impairment and adverse neurologic outcomes. There is currently no specific drug treatment for sepsis. Indole-3-guanylhydrazone hydrochloride (LQM01) is an aminoguanidine derivative that has been described as an anti-inflammatory, antihypertensive and antioxidant with potential applicability in inflammatory diseases.METHODS:
We used a LPS-challenged neonatal sepsis rodent model to investigate the effect of LQM01 on cognitive impairment and anxiety-like behavior in sepsis mice survivors, and examined the possible molecular mechanisms involved.RESULTS:
It was found that LQM01 exposure during the neonatal period reduces anxiety-like behavior and cognitive impairment caused by lipopolysaccharides (LPS) in adult life. Additionally, treatment with LQM01 decreased pro-inflammatory cytokine levels and reduced NFκB, COX-2, MAPK and microglia activation in hippocampus of neonatal mice. Furthermore, LQM01 was also able to prevent oxidative damage in hippocampus of neonatal mice and preserve brain barrier integrity.CONCLUSIONS:
LQM01 attenuated inflammatory reactions in an LPS-challenged neonatal sepsis mice model through the MAPK and NFκB signaling pathways and microglia activation suppression. All these findings are associated with mitigated cognitive impairment in 70 days-old LQM01 treated-mice. GENERALSIGNIFICANCE:
We revealed the effect of LQM01 as an anti-septic agent, and the role of crucial molecular pathways in mitigating the potential damage caused by neonatal sepsis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Guanidina
/
Disfunção Cognitiva
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Sepse Neonatal
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Indóis
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Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurochem Int
Ano de publicação:
2020
Tipo de documento:
Article