Late Anxiety-Like Behavior and Neuroinflammation in Mice Subjected to Sublethal Polymicrobial Sepsis

Calsavara, Allan Jefferson Cruz; Rodrigues, David Henrique; Miranda, Aline Silva de; Costa, Priscila A.; Lima, Cristiano Xavier; Vilela, Márcia Carvalho

doi:10.1007/s12640-012-9364-1

Cited by 46 publications

(30 citation statements)

References 29 publications

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“…Previous studies reported that LPS, at a dose of 5 mg/kg, could induce a long-lasting neuro-inflammation and showed persistent cognitive and behavioral abnormality in animals2427 which resemble the symptoms of endotoxemia related encephalopathy in patients4222324. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation and cognitive dysfunction.…”

Section: Discussionsupporting

confidence: 56%

“…For in vitro experiment dioscin was added to the serum free medium after it was dissolved in DMSO and the final concentration of dimethyl sulfoxide (DMSO) was less than 0.1%. Because previous studies have shown that LPS resulted in a long-lasting neuro-inflammation and persistent changes in neurophysiological, cognitive and behavioral parameters4222324, we administered mice with endotoxemia by an intra-peritoneal injection of LPS dissolved in saline at a dose of 10 mg/kg 24 hours before behavioral tests, while mice from control group received an equal volume of saline.…”

Section: Methodsmentioning

confidence: 99%

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Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

Yang

Chen

et al. 2017

Sci Rep

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Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation.

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Section: Discussionsupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

Yang

Chen

et al. 2017

Sci Rep

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“…Under physiological conditions, IL-1β and TNF-α play an important role in neurogenesis, synaptic plasticity, long-term potentiation (LTP) and memory formation and consolidation 19,20 . On the other hand, the over-expression of these cytokines in the CNS has been associated with behavioral and cognitive impairment in several pathological conditions 21,22,23,24 .…”

mentioning

confidence: 99%

Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

Silva

Sousa

Miranda

et al. 2015

Arq. Neuro-Psiquiatr.

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The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCA O ), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCA O were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCA O promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

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“…Animals were subjected to CLP as previously described (Calsavara et al 2013;Comim et al 2011;Wichterman et al 1980). Briefly, mice were anesthetized with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg) given intraperitoneally.…”

Section: Animals and Surgical Proceduresmentioning

confidence: 99%

TNFR1 absence protects against memory deficit induced by sepsis possibly through over-expression of hippocampal BDNF

et al. 2014

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The involvement of TNF-α type 1 receptor (TNFR1) in memory deficits induced by sepsis was explored by using TNFR1 knockout (KO) mice. We reported that wild type (WT) mice presented memory deficits in the novel object recognition test 10 days after sepsis induced by cecum ligation and perforation (CLP). These deficits were not observed in TNFR1 KO mice. The involvement of serum and brain cytokines TNF-α, IL-1β, IL-6, IFN-γ and IL-10 was then investigated. TNFR1 KO mice had higher serum levels of TNF-α and IL-1β, and brain levels of TNF-α than WT mice. After CLP, the brain levels of TNF-α, IL-1β, IL-6 and IFN-γ increased in both WT and KO mice. Our next step was to determine the expression of inflammatory cytokines, BDNF and TrKb in the hippocampus. The absence of TNFR1 in mice subjected to polymicrobial sepsis resulted in higher BDNF expression in the hippocampus. In conclusion, after CLP, memory is preserved in the absence of TNFR1. This finding was associated with increased BDNF expression in the hippocampus.

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Late Anxiety-Like Behavior and Neuroinflammation in Mice Subjected to Sublethal Polymicrobial Sepsis

Cited by 46 publications

References 29 publications

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

TNFR1 absence protects against memory deficit induced by sepsis possibly through over-expression of hippocampal BDNF

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