Toll‐like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of <scp>SE</scp>‐induced epilepsy in mice

Gross, Adi; Benninger, Felix; Madar, Ravit; Illouz, Tomer; Griffioen, Kathleen J.; Steiner, Israel; Offen, Daniel; Okun, Eitan

doi:10.1111/epi.13688

Cited by 56 publications

(28 citation statements)

References 43 publications

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“…wild‐type mice, in the absence of changes in SE severity or duration, supporting the involvement of this receptor in epileptogenesis . Recently, the contribution of TLR3 to disease progression has been reported in a mouse model of SE‐induced epilepsy .…”

Section: Il‐1r/toll‐like Receptor Signallingmentioning

confidence: 76%

Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies

Vliet

Aronica

Vezzani

et al. 2018

Neuropathology Appl Neurobio

206

142

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Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like receptor signalling, cyclooxygenase-2, tumour necrosis factor-alpha, complement signalling and chemokines. Furthermore, by drawing on evidence from preclinical and clinical studies we will discuss the potential of these signalling pathways targets for novel therapeutic interventions that control drug-resistant seizures or have disease-modifying effects. Finally, we will assess the use of these inflammatory pathways as potential biomarkers for the development of epilepsy or to measure the effectiveness of therapeutic interventions.

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Section: Il‐1r/toll‐like Receptor Signallingmentioning

confidence: 76%

Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies

Vliet

Aronica

Vezzani

et al. 2018

Neuropathology Appl Neurobio

206

142

View full text Add to dashboard Cite

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“…In children with genetic defects that shared the common feature of encoding proteins involved in TLR3 interferon signaling pathways, mutations in TLR3 were associated with recurrent HSE (Zhang et al, 2007;Lim et al, 2014;Steiner and Tyler, 2014). Whether the defect in the TLR3 receptor reduces inflammation-mediated epileptogenesis as shown in animal models needs to be established in future clinical studies (Benninger et al, 2014;Gross et al, 2017). Regarding autoimmune-mediated encephalitis, reports suggest that the most commonly recognized cause of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate receptor encephalitis, may in some cases be triggered by and follow HSE (Armangue et al, 2013(Armangue et al, , 2015.…”

Section: Prognosismentioning

confidence: 99%

CSF in acute and chronic infectious diseases

Benninger

Steiner

2018

Handbook of Clinical Neurology

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Infections of the nervous system are an important and challenging aspect of clinical neurology. Immediate correct diagnosis enables to introduce effective therapy, in conditions that without diagnosis may leave the patient with severe neurological incapacitation and sometimes even death. The cerebrospinal fluid (CSF) is a mirror that reflects nervous system pathology and can promote early diagnosis and therapy. The present chapter focuses on the CSF findings in neuro-infections, mainly viral and bacterial. Opening pressure, protein and glucose levels, presence of cells and type of the cellular reaction should be monitored. Other tests can also shed light on the causative agent: serology, culture, staining, molecular techniques such as polymerase chain reaction. Specific examination such as panbacterial and panfungal examinations should be examined when relevant. Our chapter is a guide-text that combines clinical presentation and course with CSF findings as a usuaful tool in diagnosis of neuroinfections. ACUTE INFECTIOUS DISEASES OF THE NERVOUS SYSTEMAcute infections of the nervous system are as diverse in their clinical consequences for the patient as the variety of infectious agents causing them: from mild headaches to long-term morbidity and a threat to life. Therefore, the earliest possible diagnosis is absolutely essential. Central here stands the examination of the CSF. The correct diagnosis is often dependent on this rather simple procedure to allow diagnosis and focused antimicrobial and adjunctive therapy. This chapter deals with acute infectious diseases of the nervous system and the importance of the lumbar puncture (LP) in the diagnostic process.

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“…Numerous studies have implicated inflammatory and immune response signaling in seizure onset and epileptogenesis. [1][2][3][4][5][6][7][8][9][10][11][12][13] These studies suggest that neuroinflammation is both an outcome and a contributor to seizures, and sustained neuroinflammation may play a role in the development of epilepsy. An earlier review of the relationship between inflammation and epilepsy concluded that "brain inflammation is not a mere hallmark of tissue pathology but plays an active role in sustaining or precipitating seizures."…”

Section: Introductionmentioning

confidence: 94%

“…14 The central role of proinflammatory cytokines in initiating and sustaining seizures is suggested by three main observations drawn from clinical and animal studies: (1) molecular analysis of epileptogenic human tissue often reveals elevation of pro-inflamma-tory cytokines; (2) animal studies show that induced seizures produce an inflammatory cascade mediated by cytokines; and (3) animal studies demonstrate that induction of key cytokines results in increased seizure susceptibility. Collectively, these observations form the basis of the "vicious cycle" characterization of epilepsy, 12,[15][16][17] and proinflammatory cytokines are key effectors of the cycle. These neuroinflammatory mediators have become attractive targets for the development of new therapeutic approaches for the treatment of intractable epilepsy.…”

Section: Introductionmentioning

confidence: 98%

Neuroinflammatory Nexus of Pediatric Epilepsy

Bagla

Dombkowski

2018

J Pediatr Epilepsy

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A rapidly growing body of evidence supports the premise that neuroinflammation plays an important role in initiating and sustaining seizures in a range of pediatric epilepsies. Clinical and experimental evidence indicate that neuroinflammation is both an outcome and a contributor to seizures. In this manner, seizures that arise from an initial insult (e.g. infection, trauma, genetic mutation) contribute to an inflammatory response that subsequently promotes recurrent seizures. This cyclical relationship between seizures and neuroinflammation has been described as a ‘vicious cycle.’ Studies of human tissue resected for surgical treatment of refractory epilepsy have reported activated inflammatory and immune signaling pathways, while animal models have been used to demonstrate that key inflammatory mediators lead to increased seizure susceptibility. Further characterization of the molecular mechanisms involved in this cycle may ultimately enable the development of new therapeutic approaches for the treatment of epilepsy. In this brief review we focus on key inflammatory mediators that have become prominent in recent literature of epilepsy, including newly characterized microRNAs and their potential role in neuroinflammatory signaling.

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Toll‐like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE‐induced epilepsy in mice

Abstract: This study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE.

Cited by 56 publications

References 43 publications

Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies

Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies

CSF in acute and chronic infectious diseases

Neuroinflammatory Nexus of Pediatric Epilepsy

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