Evaluation of serum high‐mobility group box 1 concentration in dogs with epilepsy: A case‐control study

Koo, Yoonhoi; Kim, Hakhyun; Yun, Taesik; Jung, Dong‐In; Kang, Ji‐Houn; Chang, Dongwoo; Na, Ki-Jeong; Yang, Mhan‐Pyo; Kang, Byeong‐Teck

doi:10.1111/jvim.15940

Cited by 6 publications

(9 citation statements)

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“…In epileptic dogs, with regard to seizure etiologies, serum HMGB1 concentrations of idiopathic epilepsy and structural epilepsy were significantly higher than those of the healthy control dogs. However, there were no significant differences between the serum HMGB1 concentrations of idiopathic versus structural epilepsy dogs ( p = .41) 13 …”

Section: Discussionmentioning

confidence: 80%

“…However, there were no significant differences between the serum HMGB1 concentrations of idiopathic versus structural epilepsy dogs (p = .41). 13 The available data therefore support that higher levels of HMGB1 in serum of drug-resistant versus drugresponsive patients are unlikely to reflect the different epilepsy types or different seizure types, but rather they likely reflect intrinsic propensity of the patient to respond or not respond to antiseizure medication.…”

Section: Discussionmentioning

confidence: 82%

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High‐mobility group box 1 as a predictive biomarker for drug‐resistant epilepsy: A proof‐of‐concept study

et al. 2021

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Drug-resistant seizures affect approximately one third of people with epilepsy. The discovery of biomarkers that can predict patients at risk of developing drug resistance is likely to be critical to the success of clinical trials of novel therapeutics for the treatment or prevention of drug resistance.Mounting evidence suggests that dysregulated neuroinflammation in brain contributes to continued seizures and disease progression in drug-resistant structural epilepsies, and may modulate seizure response to antiseizure drugs (ASDs). 1 High-mobility group box 1 (HMGB1) mediates sterile neuroinflammation evoked by epileptogenic injury and recurrent seizures. 2 HMGB1 increases in neurons, glia, and endothelial cells of the blood-brain barrier (BBB) in human drug-resistant epilepsy foci, and in corresponding animal models. 2,3 Blood levels of HMGB1 appear to mirror brain changes in animal models of acquired epilepsy. 3 Mice injected intracerebrally with HMGB1 develop more seizures in response to chemoconvulsants, whereas mice injected with anti-HMGB1 drugs or anti-HMGB1 monoclonal antibody or lacking HMGB1-activated Toll-like receptor 4 (TLR4) are less susceptible to seizures and less

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 82%

High‐mobility group box 1 as a predictive biomarker for drug‐resistant epilepsy: A proof‐of‐concept study

et al. 2021

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“…Serum IL‐1β concentrations were increased in both dogs with IE and SE compared with controls, although there was no significant difference between the IE and SE groups 23 . Furthermore, serum high‐mobility group box 1, a key mediator in neuroinflammation, was higher in epileptic dogs than in healthy dogs, although again no significant difference was found between dogs with IE and SE 24 …”

Section: Introductionmentioning

confidence: 88%

“…23 Furthermore, serum high-mobility group box 1, a key mediator in neuroinflammation, was higher in epileptic dogs than in healthy dogs, although again no significant difference was found between dogs with IE and SE. 24 There is a lack of studies investigating the behaviour of sCRP in dogs with epilepsy, despite the increased inclusion of sCRP in standard laboratory profiles. 5,25 Therefore, we aimed to investigate if there were increases in sCRP in dogs with epilepsy and to compare the sCRP concentrations between dogs with SE and dogs with IE.…”

Section: Introductionmentioning

confidence: 99%

Serum C‐reactive protein concentrations in dogs with structural and idiopathic epilepsy

Mahon¹,

Williams

Alves

2023

Veterinary Record

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BackgroundC‐reactive protein (CRP) is an acute‐phase protein produced by the liver during systemic inflammation. In humans, some epilepsies are associated with increased serum CRP (sCRP) concentrations, but this has yet to be proven in veterinary studies. Dogs with structural epilepsy (SE) and normal interictal neurological examination are hard to distinguish from dogs with idiopathic epilepsy (IE) without the use of advanced imaging.MethodsThe study included eight dogs with SE and 12 dogs with IE from a referral hospital population. This was a retrospective observational cohort study. The Mann–Whitney test was used to compare the sCRP concentrations within 24 hours of the last epileptic seizure between dogs with SE or IE.ResultsDogs with SE had higher sCRP concentrations than dogs with IE (8.9 [range <2.2–53.2] mg/L vs. <2.2 [range <2.2–6.9] mg/L; p = 0.043). Five of the eight (62%) dogs with SE had an sCRP concentration above the reference interval, compared with none of the 12 dogs with IE.LimitationsThe small sample size was the major limitation of this study. Other inflammatory causes were also not exclusively ruled out, although further clinical investigations were not indicated.ConclusionsThis study found that sCRP concentrations were higher in this cohort of dogs with SE than in those with IE. Further studies with larger cohorts of dogs are warranted to validate if sCRP can be used as an additional biomarker for SE.

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“…Indeed, inflammatory diseases of the CNS are important causes of seizures in dogs ( 242 ) and, as in humans, neuroinflammation may be involved in epileptogenesis and ictogenesis, i.e., the processes leading to epilepsy and seizures, respectively. For instance, high-mobility group box 1 (HMGB1), a key mediator of neuroinflammation with increased levels in patients with epilepsy, is significantly increased in the blood serum of epileptic dogs ( 243 ). Similarly, dogs with epilepsy had increased levels of interleukin (IL)-1β in serum regardless of the underlying cause of the disease ( 244 ).…”

Section: Pathogenesis Of Epilepsy In Dogsmentioning

confidence: 99%

Dogs as a Natural Animal Model of Epilepsy

Löscher

2022

Front. Vet. Sci.

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Epilepsy is a common neurological disease in both humans and domestic dogs, making dogs an ideal translational model of epilepsy. In both species, epilepsy is a complex brain disease characterized by an enduring predisposition to generate spontaneous recurrent epileptic seizures. Furthermore, as in humans, status epilepticus is one of the more common neurological emergencies in dogs with epilepsy. In both species, epilepsy is not a single disease but a group of disorders characterized by a broad array of clinical signs, age of onset, and underlying causes. Brain imaging suggests that the limbic system, including the hippocampus and cingulate gyrus, is often affected in canine epilepsy, which could explain the high incidence of comorbid behavioral problems such as anxiety and cognitive alterations. Resistance to antiseizure medications is a significant problem in both canine and human epilepsy, so dogs can be used to study mechanisms of drug resistance and develop novel therapeutic strategies to benefit both species. Importantly, dogs are large enough to accommodate intracranial EEG and responsive neurostimulation devices designed for humans. Studies in epileptic dogs with such devices have reported ictal and interictal events that are remarkably similar to those occurring in human epilepsy. Continuous (24/7) EEG recordings in a select group of epileptic dogs for >1 year have provided a rich dataset of unprecedented length for studying seizure periodicities and developing new methods for seizure forecasting. The data presented in this review substantiate that canine epilepsy is an excellent translational model for several facets of epilepsy research. Furthermore, several techniques of inducing seizures in laboratory dogs are discussed as related to therapeutic advances. Importantly, the development of vagus nerve stimulation as a novel therapy for drug-resistant epilepsy in people was based on a series of studies in dogs with induced seizures. Dogs with naturally occurring or induced seizures provide excellent large-animal models to bridge the translational gap between rodents and humans in the development of novel therapies. Furthermore, because the dog is not only a preclinical species for human medicine but also a potential patient and pet, research on this species serves both veterinary and human medicine.

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Evaluation of serum high‐mobility group box 1 concentration in dogs with epilepsy: A case‐control study

Cited by 6 publications

References 37 publications

High‐mobility group box 1 as a predictive biomarker for drug‐resistant epilepsy: A proof‐of‐concept study

High‐mobility group box 1 as a predictive biomarker for drug‐resistant epilepsy: A proof‐of‐concept study

Serum C‐reactive protein concentrations in dogs with structural and idiopathic epilepsy

Dogs as a Natural Animal Model of Epilepsy

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