Systemic Lipopolysaccharide Administration-Induced Cognitive Impairments are Reversed by Erythropoietin Treatment in Mice

Gao, Rong; Tang, Yuanhui; Tong, Jianhua; Yang, Jianjun; Ji, Mu‐Huo; Zhu, Shirley

doi:10.1007/s10753-015-0175-4

Cited by 23 publications

(15 citation statements)

References 31 publications

(45 reference statements)

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“…Consistent with previous studies [ 3 , 7 , 8 , 23 ], intraperitoneal injection of 5 mg/kg LPS produced an approximately 40% reduction in the freezing response in the contextual and cued fear conditioning tests, indicating that LPS impaired both hippocampus-dependent and hippocampus-independent memory [ 32 , 34 ]. In this study, intraperitoneal injection of 5 mg/kg LPS increased inflammation and Aβ accumulation along with microglial activation in the brain.…”

Section: Discussionsupporting

confidence: 89%

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice

et al. 2018

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Systemic inflammation induces brain neuronal inflammation, in turn causing acute cognitive disorders. Furthermore, neuronal inflammation is one cause of postoperative cognitive disorder (POCD) and delirium. However, no sufficiently established pharmacological treatment is available for neurocognitive inflammation. This study evaluated the possible neuroprotective effects of preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory changes in an animal model of lipopolysaccharide (LPS)-induced systemic inflammation. Adult mice were randomly divided into (1) control, (2) 2% sevoflurane preconditioning for 1 h, (3) intraperitoneal 5 mg/kg LPS injection, and (4) 2% sevoflurane preconditioning for 1 h + LPS injection groups. At 24 h after 5 mg/kg LPS injection, microglial activation based on ionized calcium-binding adapter molecule 1 (Iba-1) expression in the hippocampus was determined using immunostaining and immunoblotting. IL-1β and IL-6 immunoblotting were used as inflammation markers, and β-site of amyloid precursor protein cleaving enzyme 1 (BACE1) immunoblotting was performed to evaluate amyloid β-protein (Aβ) accumulation. Long-term cognitive impairment was evaluated using fear conditioning tests. Intraperitoneal LPS increased levels of Iba-1 (150%), inflammation markers (160%), and Aβ accumulation (350%), and sevoflurane preconditioning suppressed these increases. Systemic LPS caused learning deficits. Sevoflurane also maintained long-term memory in mice receiving LPS injection. Sevoflurane preconditioning prevented long-term memory impairment in the mouse model administered systemic LPS by decreasing excessive microglial activation, inflammation, and Aβ accumulation. This study supports the hypothesis that sevoflurane preconditioning might also be beneficial for neuronal inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

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Section: Discussionsupporting

confidence: 89%

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice

et al. 2018

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“…recognition, as well as more lasting (~30-60 d) deficits in inhibitory avoidance and forced swimming (34)(35)(36)(37)(38)(39)(40). Moreover, impaired contextual fear conditioning has emerged as a robust phenotype in post-septic animals (21,(41)(42)(43)(44)(45), but see 46). A study of CLP-surviving mice (at 1 month and 4 months post-surgery, compared with sham-operated mice) shows that they have sustained impairment in spatial memory but retain intact performance in other tasks (rotarod test, open field test and black-white alley) (10).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Models of Overwhelming Sepsis Implicate the Neural System that Encodes Contextual Fear Memory

Huerta

Robbiati

Huerta

et al. 2016

Mol Med

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Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus. Here we show that contextual fear conditioning, a form of associative memory for fear, is chronically disrupted in CLP mice when compared to SHAM-operated animals. We also find that the excitatory neurons in the basolateral nucleus of the amygdala (BLA) and the granule cells in the dentate gyrus (DG) display significantly fewer dendritic spines in the CLP group relative to the SHAM mice, although the dendritic arbors and gross morphology of the BLA and DG are comparable between the two groups. Moreover, the basal dendrites of CA1 pyramidal neurons are unaffected in the CLP mice. Taken together, our data indicate that the structural damage in the amygdalar-hippocampal network represents the neural substrate for impaired contextual fear memory in long-term sepsis survivors. Further, our data suggest that the brain injury caused by overwhelming sepsis alters the stability of the synaptic connections involved in associative fear. These results likely have implications for the emotional imbalance observed in human sepsis survivors.

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“…It has been demonstrated that the brain is one of the first organs affected during sepsis, which leads to neurological complications, such as sepsis-associated encephalopathy (2)(3)(4). Compared to the widely used lipopolysaccharide model, the CLP model is clinically relevant because it has a feature shared with human sepsis-induced cognitive impairment (4,13,14). Although many mechanisms, including oxidative stress, endothelial dysfunction, inflammation, unbalanced neurotransmission, mitochondrial dysfunction, and cell death have been implicated in the pathogenesis of sepsis-associated cognitive impairment (16)(17)(18)(19)(20), the precise mechanism remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…All behavioral tests were performed at 8:00 a.m. -11:00 a.m. in a sound-isolated room and subsequently analyzed by using a video-tracking system (Shanghai Mobile Datum Information Technology Company, Shanghai, China). All behavioral data were recorded by the same investigator who was blinded to the animal grouping as described in our previous studies (13,14).…”

Section: Methodsmentioning

confidence: 99%

Hippocampal β2‑microglobulin mediates sepsis‑induced cognitive impairment

Gao

Yang

et al. 2018

Mol Med Report

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Acute brain dysfunction is a frequent complication in sepsis patients and is associated with long‑term neurocognitive consequences and increased mortality, yet the underlying mechanism remains unclear. Emerging evidence has suggested that β2‑microglobulin [a component of major histocompatibility complex (MHC) class I molecules] is involved in cognitive dysfunction in various neurological diseases. Therefore, the present study tested the hypothesis that β2‑microglobulin in the brain also mediates sepsis‑induced cognitive impairment. In the present study, wild‑type and antigen processing 1 (Tap1)‑deficient mice (Tap1‑/‑) were subjected to cecal ligation and puncture (CLP). Survival rate, cognitive function, and biochemical analysis were performed at the indicated time points. The data revealed that CLP induced anxiety‑like behavior and impaired hippocampal‑dependent contextual memory in wild‑type mice, which was accompanied by hippocampal microglial activation, increased level of interleukin‑1β, and decreased concentrations of brain derived neurotrophic factor and postsynaptic density protein 95. Notably, it was demonstrated that Tap1‑/‑ mice with reduced cell surface expression of MHC I protected mice from anxiety‑like behavior and impaired hippocampal‑dependent contextual memory and reversed most of these biochemical parameters following sepsis development. In summary, the results of the present study suggest that β2‑microglobulin negatively regulates cognitive impairment in an animal model of sepsis induced by CLP.

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Systemic Lipopolysaccharide Administration-Induced Cognitive Impairments are Reversed by Erythropoietin Treatment in Mice

Cited by 23 publications

References 31 publications

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice

Preclinical Models of Overwhelming Sepsis Implicate the Neural System that Encodes Contextual Fear Memory

Hippocampal β2‑microglobulin mediates sepsis‑induced cognitive impairment

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