Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders

Шишкина, Г. Т.; Калинина, Т. С.; Gulyaeva, N. V.; Ланшаков, Д. А.; Дыгало, Н. Н.

doi:10.1134/s0006297921060043

Cited by 12 publications

(7 citation statements)

References 81 publications

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“…Neuroinflammation is believed to contribute to the delayed stroke-induced cell death in the hippocampus observed already 24 h after cerebral ischemia [ 23 , 24 ]. Acute alterations in gene expression can be important in stimulation of this consequence of ischemia [ 25 ]. Using MCAO to model the focal ischemia in rats and RNA-seq to identify DEGs, we aimed to further clarify molecular mechanisms mediating the pathways of the immunity/inflammatory activation in the hippocampal structure.…”

Section: Discussionmentioning

confidence: 99%

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

et al. 2021

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Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to “positive regulation of tumor necrosis factor biosynthetic process”, “cell adhesion”, “TNF signaling pathway”, and “phagosome” as compared with non-responding ones. In contrast, positive and negative “regulation of cell proliferation” and “HIF-1 signaling pathway” mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia.

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Section: Discussionmentioning

confidence: 99%

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

et al. 2021

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“…Given that the hippocampus plays a critical role in processing of spatial information and memory formation, pathological changes in the hippocampus, including neuroinflammation caused by ischemic stroke, have drawn increasing attention from researchers [ 41 ]. Stroke and Alzheimer’s disease (AD) share many common risk factors, such as hypertension, diabetes, and hyperlipidemia [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate

Wang

Zhang

et al. 2022

J Neuroinflammation

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Background Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI. Methods 83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test. Results 34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood–brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice. Conclusions Our data indicate a cause–effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.

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“…IL-33 has been proposed to play a role in the progression of several neurological diseases by modulating neuroinflammation [ 23 – 26 ]. The association of IL-33 with cognitive impairment was also demonstrated in studies of patients and animal models of neuroinflammation-related diseases [ 2 , 3 , 27 , 28 ]. IL-33 administration reversed memory deficits in APP/PS1 mice, an animal model of AD, which was associated with decreased inflammation [ 2 ].…”

Section: Introductionmentioning

confidence: 96%

Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation

et al. 2022

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With the advent of an aging society, the incidence of dementia is increasing, resulting in a vast burden on society. It is increasingly acknowledged that neuroinflammation is implicated in various neurological diseases with cognitive dysfunction such as Alzheimer’s disease, multiple sclerosis, ischemic stroke, traumatic brain injury, and central nervous system infections. As an important neuroinflammatory factor, interleukin-33 (IL-33) is highly expressed in various tissues and cells in the mammalian brain, where it plays a role in the pathogenesis of a number of central nervous system conditions. Reams of previous studies have shown that IL-33 has both pro- and anti-inflammatory effects, playing dual roles in the progression of diseases linked to cognitive impairment by regulating the activation and polarization of immune cells, apoptosis, and synaptic plasticity. This article will summarize the current findings on the effects IL-33 exerts on cognitive function by regulating neuroinflammation, and attempt to explore possible therapeutic strategies for cognitive disorders based on the adverse and protective mechanisms of IL-33.

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Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders

Cited by 12 publications

References 81 publications

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate

Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation

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