Abstract
Short chain fatty acids (SCFAs) are known to be actively involved in multiple brain disorders, but their roles in sepsis-associated encephalopathy (SAE) remain unclear. Here, we investigated the neuroprotective effects of SCFAs on SAE in mice. Male C57BL/6 mice were intragastrically pretreated with SCFAs for seven successive days, and then subjected to SAE induced by cecal ligation and puncture. The behavioral impairment, neuronal degeneration, and levels of inflammatory cytokines were assessed. The expressions of tight junction (TJ) proteins, including occludin and zoula occludens-1 (ZO-1), cyclooxygenase-2 (COX-2), cluster of differentiation 11b (CD11b), and phosphorylation of JNK and NF-κB p65 in the brain, were measured by western blot and Immunofluorescence analysis. Our results showed that SCFAs significantly attenuated behavioral impairment and neuronal degeneration, and decreased the levels of IL-1β and IL-6 in the brain of SAE mice. Additionally, SCFAs upregulated the expressions of occludin and ZO-1 and downregulated the expressions of COX-2, CD11b, and phosphorylation of JNK and NF-κB p65 in the brain of SAE mice. These findings suggested that SCFAs could exert neuroprotective effects against SAE in mice.
Highlights
Septic-associated encephalopathy (SAE) is one of the main sequelae of sepsis survivors, affecting between 8-70% of patients [1, 2]
SCFAs are known to be actively involved in multiple brain disorders, while their roles in sepsis-associated encephalopathy (SAE) remain unclear
A prospective case control study found that the behavioral results of children with SAE were significantly worse and there existed additional problems such as depression, conduct problems, psychotic behavior, and anxiety [22]
Summary
Septic-associated encephalopathy (SAE) is one of the main sequelae of sepsis survivors, affecting between 8-70% of patients [1, 2]. SAE increases the risk of mortality of patients with sepsis [3]. The pathophysiology of SAE is complex; blood–brain barrier (BBB) impairment and neuroinflammation might be the key processes in the occurrence of SAE [4,5,6]. Sepsis is often accompanied by increased permeability of BBB, which leads to SAE. Following BBB impairment, neuronal degeneration and brain edema aggravate brain injuries and neuroinflammation [7, 8]. Dysfunction of the vascular complex, including endothelial cells, astrocytes, and the blood-brain barrier, and activation of microglia result in neuroinflammation. Neuroinflammation in sepsis develops with the activation of brain endothelial cells, the increase of BBB permeability, and the increase of neutrophil infiltration; these abnormalities can lead to brain
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