Modulation of microglial phenotypes improves sepsis-induced hippocampus-dependent cognitive impairments and decreases brain inflammation in an animal model of sepsis.
Clin Sci (Lond)
; 134(7): 765-776, 2020 04 17.
Article
en En
| MEDLINE
| ID: mdl-32219335
ABSTRACT
BACKGROUND:
In order to modulate microglial phenotypes in vivo, M1 microglia were depleted by administration of gadolinium chloride and the expression of M2 microglia was induced by IL-4 administration in an animal model of sepsis to better characterize the role of microglial phenotypes in sepsis-induced brain dysfunction.METHODS:
Wistar rats were submitted to sham or cecal ligation and perforation (CLP) and treated with IL-4 or GdCl3. Animals were submitted to behavioral tests 10 days after surgery. In a separated cohort of animals at 24 h, 3 and 10 days after surgery, hippocampus was removed and cytokine levels, M1/M2 markers and CKIP-1 levels were determined.RESULTS:
Modulation of microglia by IL-4 and GdCl3 was associated with an improvement in long-term cognitive impairment. When treated with IL-4 and GdCl3, the reduction of pro-inflammatory cytokines was apparent in almost all analyzed time points. Additionally, CD11b and iNOS were increased after CLP at all time points, and both IL-4 and GdCl3 treatments were able to reverse this. There was a significant decrease in CD11b gene expression in the CLP+GdCl3 group. IL-4 treatment was able to decrease iNOS expression after sepsis. Furthermore, there was an increase of CKIP-1 in the hippocampus of GdCl3 and IL-4 treated animals 10 days after CLP induction.CONCLUSIONS:
GdCl3 and IL-4 are able to manipulate microglial phenotype in an animal models of sepsis, by increasing the polarization toward an M2 phenotype IL-4 and GdCl3 treatment was associated with decreased brain inflammation and functional recovery.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Conducta Animal
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Interleucina-4
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Cognición
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Microglía
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Sepsis
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Encefalitis
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Disfunción Cognitiva
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Gadolinio
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Hipocampo
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Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Sci (Lond)
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil