Abnormal neuronal damage and inflammation in the hippocampus of kainic acid‐induced epilepsy mice

Li, Xiaoying; Yang, Ciqing; Shi, Ya-Zhou; Guan, Lihong; Liang, Han; Li, Shuanqing; Li, Yunxiao; Zhang, Yong; Lin, Juntang

doi:10.1002/cbf.3651

Cited by 21 publications

(10 citation statements)

References 24 publications

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“…Epilepsy is frequently accompanied by severe histopathological hippocampal damage. , Therefore, in this work, hematoxylin and eosin (H&E) staining was applied to assess the extent of brain tissue damage in each group (Figure E–H). The control group had a distinct hierarchical structure and an orderly arrangement of nerve cells.…”

Section: Resultsmentioning

confidence: 99%

Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy

et al. 2023

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Ferroptosis is an iron-regulated, caspase-mediated pathway of cell death that is associated with the excessive aggregation of lipid-reactive oxygen species and is extensively involved in the evolution of many diseases, including epilepsy. The superoxide anion (O2 •–), as the primary precursor of ROS, is closely related to ferroptosis-mediated epilepsy. Therefore, it is crucial to establish a highly effective and convenient method for the real-time dynamic monitoring of O2 •– during the ferroptosis process in epilepsy for the diagnosis and therapy of ferroptosis-mediated epilepsy. Nevertheless, no probes for detecting O2 •– in ferroptosis-mediated epilepsy have been reported. Herein, we systematically conceptualized and developed a novel near-infrared (NIR) fluorescence probe, NIR-FP, for accurately tracking the fluctuation of O2 •– in ferroptosis-mediated epilepsy. The probe showed exceptional sensitivity and outstanding selectivity toward O2 •–. In addition, the probe has been utilized effectively to bioimage and evaluate endogenous O2 •– variations in three types of ferroptosis-mediated epilepsy models (the kainic acid-induced chronic epilepsy model, the pentylenetetrazole-induced acute epilepsy model, and the pilocarpine-induced status epilepticus model). The above applications illustrated that NIR-FP could serve as a reliable and suitable tool for guiding the accurate diagnosis and therapy of ferroptosis-mediated epilepsy.

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Section: Resultsmentioning

confidence: 99%

Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy

et al. 2023

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“…It is well-recognized that GFAP elevation is the first step of astrocyte hypertrophy in epilepsy (Savaş et al, 2021;Li et al, 2021). And the activation of JAK2/STAT3 signaling has been indicated to induce the formation of GFAP -positive glia (Lee et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A new identified COL4A2 mutation contributes to astrocyte activation by activating JAK/STAT signaling in epilepsy

Wang

2022

Preprint

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COL4A2 is the encoding gene of the α2 chains of type IV collagen, and missense mutations of COL4A2 is correlated with multiple diseases. However, the association of COL4A2 mutations with epilepsy remains elusive. Here, we aimed to explore the function of COL4A2 mutations in the development of epilepsy. We performed a full spectrum of family-enhanced whole-exome sequencing on a family lineage and examined the genetic change on COL4A2 gene. The kainic acid (KA)-induced in vivo model and lipopolysaccharide (LPS)-induced in vitro model were established. The production and secretion of inflammation cytokines were measured by qPCR, western blotting, and ELISA assay. Neuron damages and astrocyte activation were checked by Nissle and GFAP immunofluorescence staining. One heterozygous variant was detected in the COL4A2 gene: c.1148C>T(p.Pro383Leu). COL4A2 mutation significant induced the exacerbation of seizures and impaired the learning and memory phenotype of the KA rats. COL4A2 mutation promoted the hippocampal astrocyte activation, enhanced hippocampal neuronal injury in the rats. The levels of iNOS, COX-2, IL-1β, IL-6, and TNF-α elevated in KA-treated rats and LPS-treated astrocytes were further induced by COL4A2 mutation. Mechanically, COL4A2 mutation stimulated JAK/STAT signaling. JAK2 and STAT3 phosphorylation was promoted by COL4A2 mutation and JAK/STAT signaling inhibitor WP1066 could blocked the effect in primary astrocytes and CTX-TNA cells. These data indicated that a new identified COL4A2 mutation contributed to astrocyte activation by activating JAK/STAT signaling in epilepsy. Our findings provided a novel mechanism and treatment target of COL4A2 related epilepsy.

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“…We established a mouse model of kainic acid (KA)-induced epilepsy ( 27 ). Anesthetized 4-week-old mice were intraperitoneally injected with 20 mg/kg KA ( 28 ), while control mice were injected with saline. At least one behavioral spontaneous recurrent motor seizure observed 28 d after injection was considered a successful model of chronic epilepsy.…”

Section: Methodsmentioning

confidence: 99%

Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data

Luo¹,

Han²,

Chen³

et al. 2023

Transl Pediatr

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Background Epilepsy is a chronic disease that is characterized by transient brain dysfunction caused by an abrupt abnormal neuronal discharge. Recent studies have indicated that the pathways related to inflammation and innate immunity play significant roles in the pathogenesis of epilepsy, suggesting an interrelationship between immunity and inflammatory processes and epilepsy. However, the immune-related mechanisms are still not precisely understood; therefore, this study aimed to explore the immune-related mechanisms in epilepsy disorders, highlight the role of immune cells at the molecular level in epilepsy, and provide therapeutic targets for patients with epilepsy. Methods Brain tissue samples from healthy and epileptic individuals were collected for transcriptome sequencing to identify differentially expressed genes (DEGs) and differentially expressed (DE)-long coding RNAs (lncRNAs). Based on interactions from the miRcode, starBase2.0, miRDB, miRTarBase, TargetScan, and ENCORI databases, a lncRNA-associated competitive endogenous RNA (ceRNA) network was created. Gene ontology and the Kyoto encyclopedia of genes analyses established that the genes in the ceRNA network were mainly enriched in immune-related pathways. Immune cell infiltration, screening, and protein-protein interaction analyses of the immune-related ceRNAs, and correlation analysis between immune-related core messenger RNA (mRNA) and immune cells were also performed. Results Nine hub genes ( EGFR, GRB2, KRAS, FOS, ESR1, MAPK1, MAPK14, MAPK8, and PPARG ) were obtained. Also, 38 lncRNAs, one miRNA ( hsa-miR-27a-3p ), and one mRNA ( EGFR ) comprised the final core ceRNA network. Mast cells, plasmacytoid dendritic cells, and immature dendritic cells all showed positive correlations with EGFR, while Cluster of differentiation 56 dim natural killer cells (CD56dim natural killer cells) showed negative correlations. Finally, we employed an epilepsy mouse model to validate EGFR , which is consistent with disease progression. Conclusions In conclusion, the pathophysiology of epilepsy was correlated with EGFR . Thus, EGFR could be a novel biomarker of juvenile focal epilepsies, and our findings provide promising therapeutic targets for epilepsy.

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Abnormal neuronal damage and inflammation in the hippocampus of kainic acid‐induced epilepsy mice

Cited by 21 publications

References 24 publications

Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy

Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy

A new identified COL4A2 mutation contributes to astrocyte activation by activating JAK/STAT signaling in epilepsy

Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data

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