Inflammation as a target for the treatment of fever-associated epilepsy in zebrafish larvae

Liang, Wenpeng; Wang, Jie; Sui, Jiahui; Yun, Feng; Shen, Yuntian; Zhou, Jing; Wu, Youjia; Shen, Dingding; Zhang, Qi

doi:10.1016/j.intimp.2023.109802

Cited by 6 publications

(5 citation statements)

References 55 publications

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“…Our previous research has found increased inflammatory factors in mutant GABRG2 transgenic zebrafish 8 . Proinflammatory factors, such as IL‐1β, IL‐6, TNF‐α, and TGF‐β, were reported to play important roles in epileptogenesis, 23–25 indicating that inflammatory response in the brain is a crucial mechanism in the pathophysiology of epilepsy 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Our previous research has found increased inflammatory factors in mutant GABRG2 transgenic zebrafish. 8 Proinflammatory factors, such as IL‐1β, IL‐6, TNF‐α, and TGF‐β, were reported to play important roles in epileptogenesis, 23 , 24 , 25 indicating that inflammatory response in the brain is a crucial mechanism in the pathophysiology of epilepsy. 26 The activation of inflammatory response might destroy the balance between glutamate and GABA, leading to the increase of excitability in the nervous system and seizure activity.…”

Section: Discussionmentioning

confidence: 99%

“…Previous research has indicated that neuroinflammation is involved in epileptogenesis 7 . We have also demonstrated that neuroinflammation was induced in febrile seizures, and the increased pro‐inflammatory factors, such as interleukin 1β (IL‐1β) and IL‐6, might be responsible for the epileptogenesis in fever‐associated epilepsy 8 . Increased pro‐inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α), IL‐1β, and IL‐6 were also observed in an epilepsy mouse model with Gabrg2 +/Q390X knockin, indicating neuroinflammation was one of the mechanisms for genetic epilepsy 9 .…”

Section: Introductionmentioning

confidence: 92%

“… 7 We have also demonstrated that neuroinflammation was induced in febrile seizures, and the increased pro‐inflammatory factors, such as interleukin 1β (IL‐1β) and IL‐6, might be responsible for the epileptogenesis in fever‐associated epilepsy. 8 Increased pro‐inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α), IL‐1β, and IL‐6 were also observed in an epilepsy mouse model with Gabrg2 +/Q390X knockin, indicating neuroinflammation was one of the mechanisms for genetic epilepsy. 9 However, whether neuroinflammation is involved in other phenotypes of epilepsy induced by GABRG2 mutations and is related to the severity of epilepsy needs further exploration.…”

Section: Introductionmentioning

confidence: 99%

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Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations

Sui,

Zhan,

et al. 2024

CNS Neurosci Ther

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ObjectiveTo explore the mechanism involved in variable phenotypes of epilepsy models induced by γ‐aminobutyric acid type A γ2 subunit (GABRG2) mutations.MethodsThe zebrafish carrying wild‐type (WT) GABRG2, mutant GABRG2(P282S), GABRG2(F343L) and GABRG2(I107T) were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video‐Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio‐signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different GABRG2 mutations.ResultsThe established Tg(hGABRG2P282S) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in Tg(hGABRG2P282S) zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of Tg(hGABRG2P282S) zebrafish. In addition, the behavioral activity, production of pro‐inflammatory factors, and activation of the IL‐2 receptor signal pathway varied among the three mutant zebrafish lines.ConclusionWe successfully established transgenic zebrafish epileptic models expressing human mutant GABRG2(P282S), in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS/JAK/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by GABRG2 mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations

Sui,

Zhan,

et al. 2024

CNS Neurosci Ther

Self Cite

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“…For instance, the aspect of the effect of external temperature on seizure threshold has been assessed in adult ZF, which were exposed to water temperature up to 30 • , showing a higher proneness to seizures by PTZ in parallel with a modified effect of pretreatment with glutamatergic receptor antagonists on those seizures [102]. Very recently, hyperthermia has been used to reduce seizure threshold to PTZ also in larval ZF, and it has been shown that this is associated with the production of proinflammatory cytokines in line with what is hypothesized to occur in human febrile seizures [103].…”

Section: Other Types Of Epilepsy Models In Zfmentioning

confidence: 99%

Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions

d’Amora

Galgani

Marchese

et al. 2023

IJMS

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This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation.

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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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Inflammation as a target for the treatment of fever-associated epilepsy in zebrafish larvae

Cited by 6 publications

References 55 publications

Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations

Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations

Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions

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

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