Lipopolysaccharide (LPS) increases susceptibility to epilepsy via interleukin-1 type 1 receptor signaling

Hu, Ankang; Yuan, Honghua; Qin, Ying; Zhu, Yuhua; Zhang, Lingzhi; Chen, Quangang; Wu, Lianlian

doi:10.1016/j.brainres.2022.148052

Cited by 7 publications

(3 citation statements)

References 55 publications

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“…The promoting effects of neuroin ammation, oxidative stress, and glial proliferation on the pathogenesis of epilepsy have been reported by many studies [9,18,50,51]. Among them, neuroin ammation has been proven to increase neuronal excitability by activating TLR4 and its downstream NF-kappa B, AP-1, improving blood-brain barrier permeability and secondary glial proliferation, and destroying the homeostasis of the central nervous system to enhance seizure susceptibility [14,17,22,52].…”

Section: Discussionmentioning

confidence: 99%

“…Neuroin ammation and oxidative stress belong to the immune response of the body, they widely exist in the central nervous system and affect and promote each other [6]. They jointly affect the excitability of neurons in the central nervous system and seizure susceptibility [7][8][9][10]. Microglia and astrocytes, as immune and phagocytic cells of the central nervous system, participate in the immune response to neuroin ammation of the body through self-proliferation and activation and conversion of proin ammatory and anti-in ammatory types [9,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…They jointly affect the excitability of neurons in the central nervous system and seizure susceptibility [7][8][9][10]. Microglia and astrocytes, as immune and phagocytic cells of the central nervous system, participate in the immune response to neuroin ammation of the body through self-proliferation and activation and conversion of proin ammatory and anti-in ammatory types [9,[11][12][13]. Studies have shown that acute hypoxia can cause the phosphorylation of NADPH oxidase (NOX), an oxidative stress product, and can also induce oxidative stress and neuroin ammation by increasing the expression of inducible nitric oxide synthase (iNOX), promoting active oxygen species (ROS), cyclooxygenase 2 (COX-2), and prostaglandin E2 (PGE2) [14,15], thereby activating microglia and transforming them into M1 type proin ammatory microglia [13].…”

Section: Introductionmentioning

confidence: 99%

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Long-term intervention at high altitudes can inhibit the expression of IBA-1 in the hippocampus of rats and reduce seizure susceptibility

Fan

2022

Preprint

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Tens of millions of people around the world are affected by high-altitude hypoxia and epilepsy. Previous studies have shown that high-altitude hypobaric hypoxia can affect the homeostasis of the human central nervous system. However, there are no related studies on the excitability of human neurons and seizure susceptibility to natural high-altitude hypoxia. By using the natural experimental site on the Qinghai-Tibet Plateau, our team studied the pathological changes and seizure susceptibility in the hippocampus of rats under the long-term intervention of hypobaric hypoxia on the natural plateau from the aspects of protein expression, histomorphology, and animal behavior. and the linear correlation between the above changes was confirmed by statistical methods. This study is helpful to explore the mechanism of hypoxia adaptation at high altitudes and further clarifies the pathogenesis of epilepsy and has practical significance to explore the regional characteristics of potential epilepsy, antiepileptic drug therapy, and non-drug treatment of epilepsy. Objectives: Epilepsy is caused by highly synchronized abnormal discharge of brain neurons. At present, its specific pathogenesis has not been clarified. However, the initial event of most epileptic seizures can be seen as an abnormal increase in neuronal excitability, neuroinflammation, oxidative stress, and damage-related molecular models (such as reactive oxygen species from oxidative stress products, activated M1 proinflammatory microglia, high mobility group box-1, etc.) are involved in neuronal loss, decreased excitation threshold and increased seizure susceptibility. In this study, we explored the changes of glial cell activation markers GFAP and IBA-1, the expression of AQP4 at the end of astrocytes, and the number of neurons in the hippocampus of SD rats under the long-term intervention of natural environment at high altitude, and analyzed the correlation between the above changes and the seizure susceptibility in rats. The aim was to study the linear relationship between the changes of hippocampal glial cell activation markers GFAP, IBA-1, AQP-4, hippocampal CA1, CA3, DG neurons, and seizure susceptibility in rats under the long-term intervention of natural hypobaric hypoxia at high altitude. Methods: Three-week-old SD rats were exposed to the natural hypobaric hypoxia environment at a high altitude (Maduro County, Tibetan Autonomous Region, Golog Prefecture, Qinghai Province, China, 4260m above sea level) for 25 weeks. The control group rats were raised on the plain (Xi’an, Shanxi Province, China) for 25 weeks, and then epilepsy modeling, seizure susceptibility assessment, brain tissue sampling, immunohistochemical staining, Nissl staining, and other tests. In the first stage of the experiment, we studied the effects of different altitudes on the expression levels of astrocyte marker GFAP, astrocyte terminal foot AQP-4, microglial marker IBA-1, and the number of neurons in hippocampal CA1, CA3, DG regions of SD rats, and evaluated their seizure susceptibility, and analyzed the difference in seizure susceptibility of rats in each group and the linear correlation between them and the number of hippocampal GFAP, IBA-1, AQP4, and neurons. In the second stage of the experiment, we used trehalose and acetazolamide to inhibit the expression of GFAP, IBA-1, and AQP-4 in rats of high altitude hypoxia group for a long time respectively, and compared their seizure susceptibility with rats of high altitude hypoxia group to further clarify the relationship between the expression changes of GFAP, IBA-1, AQP4 and seizure susceptibility. Results: Compared with the rats in the plain control group, long-term natural hypobaric hypoxia at high altitudes can reduce the expression of GFAP, IBA-1, and AQP4 in the hippocampus of SD rats, increase the number of neurons in the DG area of the hippocampus, prolong the latency of the first seizure of SD rats, reduce the total seizure grade score of SD rats (reduce the seizure susceptibility of SD rats), and the change in the expression of IBA-1 has a linear correlation with the difference in the seizure susceptibility of SD rats. In addition, long-term application of trehalose to the natural plateau environment intervention group can prolong the incubation period of the first attack of SD rats, and further reduce the expression of IBA-1 in the hippocampus of SD rats, but the difference is not statistically significant. Our study shows that long-term intervention in high altitude natural hypobaric hypoxia environment may reduce the expression of GFAP, IBA-1, and AQP-4 in the hippocampus and increase the number of neurons in the hippocampal DG region of SD rats by inhibiting neuroinflammation, oxidative stress, glial proliferation, cell swelling, and neuronal loss, and reduce the seizure susceptibility, in which the change of IBA-1 expression is involved in the process of seizure susceptibility. This study shows that long-term intervention in a natural hypobaric hypoxia environment at high altitudes may have a protective effect on brain tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term intervention at high altitudes can inhibit the expression of IBA-1 in the hippocampus of rats and reduce seizure susceptibility

Fan

2022

Preprint

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Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

Yu,

Sun

2024

Ibrain

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Epilepsy is an abnormal neurologic disorder distinguished by the recurrent manifestation of seizures, and the precise underlying mechanisms for its development and progression remain uncertain. In recent years, the hypothesis that inflammatory mediators and corresponding pathways contribute to seizures has been supported by experimental results. The potential involvement of neuroinflammation in the development of epilepsy has garnered growing interest. This review centers attention on the involvement of inflammatory mediators in the emergence and progression of epilepsy within recent years, focusing on both clinical research and animal models, to enhance comprehension of the intricate interplay between brain inflammation and epileptogenesis.

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MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation

Liu,

Xue

et al. 2024

Mol Biol Rep

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Background Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. Methods Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. Results The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. Conclusions Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis. Graphical Abstract

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Lipopolysaccharide (LPS) increases susceptibility to epilepsy via interleukin-1 type 1 receptor signaling

Cited by 7 publications

References 55 publications

Long-term intervention at high altitudes can inhibit the expression of IBA-1 in the hippocampus of rats and reduce seizure susceptibility

Long-term intervention at high altitudes can inhibit the expression of IBA-1 in the hippocampus of rats and reduce seizure susceptibility

Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy

MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation

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