High mobility group box 1 in the inflammatory pathogenesis of epilepsy: profiling circulating levels after experimental and clinical seizures

Walker, L. R.; Tse, Karen; Ricci, Emanuele; Thippeswamy, Thimmasettappa; Sills, Graeme J.; White, Steve H.; Antoine, Daniel J.; Marson, Anthony G; Pirmohamed, Munir

doi:10.1016/s0140-6736(14)60368-8

Cited by 15 publications

(12 citation statements)

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“…An increase in the release of pro-inflammatory cytokines, such as IL-1b, contributes to the generation of human febrile seizures and potentially induces long-lasting hyperexcitability and excitotoxicity that is associated with hippocampal epilepsy (Dube et al, 2005;Vezzani et al, 1999). Increases in HMGB1 might occur as a consequence of seizures (Choi et al, 2011;Maroso et al, 2010;Walker et al, 2014), which is consistent with our results that HMGB1 expression levels were elevated in the mouse hippocampus and cortex. Expression levels of IL-1b and HMGB1 in our experiments indicated that it was dependent upon TRPV1 activation (as no change was observed in IL-1b and HMGB1 release in the TRPV1 knockout mice).…”

Section: Discussionsupporting

confidence: 91%

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain

Huang

Sánchez

et al. 2015

Brain, Behavior, and Immunity

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Section: Discussionsupporting

confidence: 91%

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain

Huang

Sánchez

et al. 2015

Brain, Behavior, and Immunity

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“…) as well as in clinical studies (Walker et al . ). On the contrary, decreased brain HMGB1 levels and increased plasma HMGB1 levels have also been reported in pilocarpine‐treated mice (Fu et al .…”

Section: Challenges Of Hmgb1 As a Therapymentioning

confidence: 97%

“…Moreover, the current findings regarding the expression level of HMGB1 in epileptic subjects is contradictory deserving further extensive investigations. A number of studies have reported an elevated expression level of HMGB1 in pilocarpine (Yang et al 2017) and KA-induced seizure models in immature experimental animals (Morales-Sosa et al 2018) as well as in clinical studies (Walker et al 2014). On the contrary, decreased brain HMGB1 levels and increased plasma HMGB1 levels have also been reported in pilocarpine-treated mice (Fu et al 2017) which lends credence to the idea that HMGB1 translocate from cell nuclei to the surrounding areas, including the bloodstream, after pilocarpine administration (Fu et al 2017).…”

Section: Challenges Of Hmgb1 As a Therapymentioning

confidence: 99%

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

Paudel

Semple

Jones

et al. 2019

Journal of Neurochemistry

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Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti‐epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high‐mobility group box protein 1 (HMGB1), a DNA‐binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1‐targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development.

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“…Thus, HMGB1/RAGE/TLR4 signaling might contribute toward the generation and perpetuation of seizures ( Figure 4 ) in humans and can be successfully targeted to attain anti-convulsant effects in epilepsies which are resistant to drugs. The expression level of HMGB1 was significantly elevated in the hippocampus and cortex after 24-h in a KA-induced model of SE, which suggests that the HMGB1 protein has a key role in epilepsy ( Walker et al, 2014 ). HMGB1 enhances hypothermia induced seizures and contributes to the pathogenesis of febrile seizure.…”

Section: Role Of Hmgb1 In Epilepsymentioning

confidence: 99%

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

et al. 2018

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High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein released by glia and neurons upon inflammasome activation and activates receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR) 4 on the target cells. HMGB1/TLR4 axis is a key initiator of neuroinflammation. In recent days, more attention has been paid to HMGB1 due to its contribution in traumatic brain injury (TBI), neuroinflammatory conditions, epileptogenesis, and cognitive impairments and has emerged as a novel target for those conditions. Nevertheless, HMGB1 has not been portrayed as a common prognostic biomarker for these HMGB1 mediated pathologies. The current review discusses the contribution of HMGB1/TLR4/RAGE signaling in several brain injury, neuroinflammation mediated disorders, epileptogenesis and cognitive dysfunctions and in the light of available evidence, argued the possibilities of HMGB1 as a common viable biomarker of the above mentioned neurological dysfunctions. Furthermore, the review also addresses the result of preclinical studies focused on HMGB1 targeted therapy by the HMGB1 antagonist in several ranges of HMGB1 mediated conditions and noted an encouraging result. These findings suggest HMGB1 as a potential candidate to be a common biomarker of TBI, neuroinflammation, epileptogenesis, and cognitive dysfunctions which can be used for early prediction and progression of those neurological diseases. Future study should explore toward the translational implication of HMGB1 which can open the windows of opportunities for the development of innovative therapeutics that could prevent several associated HMGB1 mediated pathologies discussed herein.

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High mobility group box 1 in the inflammatory pathogenesis of epilepsy: profiling circulating levels after experimental and clinical seizures

Cited by 15 publications

References 0 publications

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

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