Time courses of HMGB1 and other inflammatory markers after generalized convulsive seizures

Nass, Robert D.; Wagner, Marcus; Surges, Rainer; Holdenrieder, Stefan

doi:10.1016/j.eplepsyres.2020.106301

Cited by 34 publications

(33 citation statements)

References 26 publications

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“…These proteins can be released to the extracellular media, reaching CSF and blood. In this sense, S100β levels have been proposed as a biomarker of neurological disorders, and it has been observed that the levels of S100β in serum increased in patients who experienced unfavorable seizure outcomes [87,88].…”

Section: Relationship Between Reactive Astrocytes and Microglia In Nementioning

confidence: 99%

“…These processes are mediated by the presence of "find-me" signals of neuronal origin (e.g., ATP and other nucleotides, fractalkine, etc.) which attract and are recognized by microglial receptors (e.g., purinergic P2 × 7 receptor for ATP, CX3CR1 for fractalkine) [86][87][88][89][90][91][92][93][94]. Neuronal cells ready to be eliminated are also decorated on the external phase of their plasma membrane with "eat-me" signals such as C3, C1q, phosphatidylserine (PS), or ApoE, which are recognized by microglial CR3/Cd11b receptor (for complement proteins) and TREM2 (triggering receptor expressed on myeloid cells 2)/DAP12 (DNAX Adaptor Protein 12) and MerTk (MER tyrosine kinase) receptors (for PS).…”

Section: Relationship Between Reactive Astrocytes and Microglia In Nementioning

confidence: 99%

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Reactive Glia Inflammatory Signaling Pathways and Epilepsy

Sanz

García-Gimeno

2020

IJMS

110

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Neuroinflammation and epilepsy are interconnected. Brain inflammation promotes neuronal hyper-excitability and seizures, and dysregulation in the glia immune-inflammatory function is a common factor that predisposes or contributes to the generation of seizures. At the same time, acute seizures upregulate the production of pro-inflammatory cytokines in microglia and astrocytes, triggering a downstream cascade of inflammatory mediators. Therefore, epileptic seizures and inflammatory mediators form a vicious positive feedback loop, reinforcing each other. In this work, we have reviewed the main glial signaling pathways involved in neuroinflammation, how they are affected in epileptic conditions, and the therapeutic opportunities they offer to prevent these disorders.

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Section: Relationship Between Reactive Astrocytes and Microglia In Nementioning

confidence: 99%

Section: Relationship Between Reactive Astrocytes and Microglia In Nementioning

confidence: 99%

Reactive Glia Inflammatory Signaling Pathways and Epilepsy

Sanz

García-Gimeno

2020

IJMS

110

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“…Anti-HMGB1 mAb therapy or HMGB1-release inhibitors may provide an alternative approach to the control of epilepsy and epileptogenesis [114,115]. Nass et al [116] determined the plasma levels of HMGB1, MMP-9, and ICAM-1 after a single generalized convulsive seizure in epileptic patients. They observed a significant elevation of all these factors and suggested the presence of brain inflammation with BBB disruption even after a single seizure.…”

Section: Epilepsy and Bbb Disruptionmentioning

confidence: 99%

High Mobility Group Box-1 and Blood–Brain Barrier Disruption

Nishibori

Wang

Ousaka

et al. 2020

Cells

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Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.

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“…Over the past decades, the inflammatory and immune responses have been suspected of participating in one of the potential underlying mechanisms for epilepsy (17,18), and intravenous immune globulin has subsequently been used in the treatment of intractable childhood epilepsy. Immune (19)(20)(21)(22), and a relationship has been identified between HLA and epilepsy (23)(24)(25)(26). Furthermore, CXCL1 has an association with epilepsy (27); however, the actual roles of HLA-C and CXCL1 in epilepsy have remained obscure.…”

Section: Discussionmentioning

confidence: 99%

Identification of significant immune-related genes for epilepsy via bioinformatics analysis

Luo¹,

Xiang²,

Huang³

et al. 2021

Ann Transl Med

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Background: Epilepsy is one of the most common neurological disorders, but its underlying mechanism has remained obscure, and the role of immune-related genes (IRGs) in epilepsy have not yet been investigated.Therefore, in this study, we explored the association between IRGs and epilepsy.Methods: An IRG list was collected from the ImmPort database. The gene expression profiles of GSE143272 were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm. nih.gov/geo/). Differentially expressed genes (DEGs) between epilepsy and normal samples were analyzed, and the intersections between IRGs and DEGs were identified using the VennDiagram package, with the intersected genes subjected to further analysis. Enrichment function for intersected genes were performed, constructed a protein-protein interaction (PPI) network via the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes (top 10) of the PPI network were calculated by the cytoHubba plug-in in Cytoscape. The top correlated genes were selected to perform correlation analysis with immune cells infiltration and expression levels. Finally, we performed validation of the top correlated genes transcriptional expression levels using an animal model.Results: There were a total of 245 DEGs detected in GSE143272, among which 143 were upregulated and 102 downregulated genes in epilepsy. A total of 44 differential IRGs were obtained via intersection of DEGs and IRGs. Enrichment function analysis of DEGs showed that they played a significant role in immune response. The gene CXCL1 was the most correlated with other differentially expressed IRGs via the PPI network. The results of immune cell infiltration analysis indicated that epilepsy patients had higher activated mast cells infiltration (P=0.021), but lower activated CD4 memory T cells (P=0.001), resting CD4 memory T cells (P=0.011), and gamma delta T cells (P=0.038) infiltration. It was revealed that CXCL1 and activated mast cells (R=0.25, P=0.019) and neutrophils (R=0.3, P=0.0043), and a negative correlation with T cells gamma delta (R=−0.25, P=0.018). The levels of CXCL1 expression were significantly lower in epilepsy patients than those in normal samples.Conclusions: In this study, the results showed that IRGs such as CXCL1 have a significant influence on epilepsy via regulation of immune cells infiltration.

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Time courses of HMGB1 and other inflammatory markers after generalized convulsive seizures

Cited by 34 publications

References 26 publications

Reactive Glia Inflammatory Signaling Pathways and Epilepsy

Reactive Glia Inflammatory Signaling Pathways and Epilepsy

High Mobility Group Box-1 and Blood–Brain Barrier Disruption

Identification of significant immune-related genes for epilepsy via bioinformatics analysis

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