Novel Concepts in Epileptogenesis and its Prevention

Jehi, Lara; Vezzani, Annamaria

doi:10.1007/s13311-014-0268-z

Cited by 9 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, development of new AEDs and new methods/approaches to treatment are urgently required. Furthermore, most evidence supports the view that development of epilepsy (epileptogenesis) is a process that should be treated as early and effectively as possible to try to prevent the development of chronic, intractable epilepsy; therefore, there is an urgent need to find ways to prevent the development of disease in individuals at risk (Jehi and Vezzani, 2014). Epileptogenesis refers to a dynamic process that progressively alters neuronal excitability, establishes critical (abnormal) synaptic interconnections, and perhaps requires intricate structural/biochemical changes before the first spontaneous seizure occurs (Pitkänen and Engel, 2014).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis

Citraro

Iannone

Leo

et al. 2019

Brain Research Bulletin

View full text Add to dashboard Cite

Liraglutide (LIR) is a novel long-lasting glucagon-like peptide-1 (GLP-1) analogue that facilitates insulin signalling and shows also neuroprotective properties in different brain disease models. In this study, we explored the potential antiepileptogenic effects of LIR in two different animal models; namely, the mouse intrahippocampal kainic acid (KA) model of temporal lobe epilepsy and the WAG/Rij rat model of absence epileptogenesis. Moreover, we evaluated LIR effects on comorbidities in various behavioural tests. Mice with kainate-induced epilepsy were treated with LIR (300 g/kg/day s.c.) for 4 weeks after status epilepticus and then evaluated for drug effects on seizure development and behavioural alterations, whereas WAG/Rij rats were treated for 17 weeks (starting at 30 days of age, before seizure onset) with LIR (300 µg/kg/day s.c.) in order to investigate whether an early chronic treatment was able to reduce the development of absence seizures and related comorbidities. Our results indicate that LIR was effective in reducing the development of spontaneous seizures in kainate-induced epilepsy; moreover, in this model, it prevented memory impairment and related anxiety-like behaviour in the open field (OF) test while in the forced swimming test (FST), LIR displayed an apparent pro-depressant effect that was instead related to reduced endurance as confirmed by rotarod test. In contrast, LIR was unable to modify the epileptogenic process underlying the development of absence seizures in WAG/Rij rats while being antidepressant in the FST in this strain. Our results indicate that LIR may represent a promising novel treatment to prevent and treat the epileptogenic process and its associated behavioural and cognitive alterations in some models of convulsive epilepsy characterized by neurodegeneration, since LIR effects are likely secondary to its recognised neuroprotective properties.

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis

Citraro

Iannone

Leo

et al. 2019

Brain Research Bulletin

View full text Add to dashboard Cite

show abstract

“…Epileptogenesis refers to the pathological process of a brain from its normal situation to the neuron network alterations following initial insults, which can produce continuous prone of unprovoked spontaneous seizures [ 26 , 27 ]. The precipitating epileptogenic events (PEEs) vary over a wide range including stroke, TBI, neurodegenerative diseases, infectious and autoimmune disorders, prolonged febrile convulsions, as well as some specific genetic conditions [ 28 ].…”

Section: Concepts Of Epileptogenesis and Antiepileptogenic Drugsmentioning

confidence: 99%

How to Find Candidate Drug-targets for Antiepileptogenic Therapy?

Lin

Qin

2020

View full text Add to dashboard Cite

: Although over 25 antiepileptic drugs (AEDs) have become currently available for clinical use, the incidence of epilepsy worldwide and the proportions of drug-resistant epilepsy among them are not significantly reduced during the past decades. Traditional screens for AEDs have been mainly focused on their anti-ictogenic roles, and their efficacies primarily depend on suppressing neuronal excitability or enhancing inhibitory neuronal activity, almost without the influence on the epileptogenesis or with inconsistent results from different studies. Epileptogenesis refers to the pathological process of a brain from its normal status to the alterations with the continuous prone of unprovoked spontaneous seizures after brain insults, such as stroke, traumatic brain injury, CNS infectious and autoimmune disorders, and even some specific inherited conditions. Recently growing experimental and clinical studies have discovered the underlying mechanisms for epileptogenesis, which are multiaspect and multistep. These findings provide us a number of interesting sites for antiepileptogenic drugs (AEGDs). AEGDs have been evidenced as significantly roles of postponing or completely blocking the development of epilepsy in experimental models. The present review will introduce potential novel candidate drug-targets for AEGDs based on the published studies.

show abstract

“…Temporal lobe epilepsy is one of the most common forms of refractory epilepsy and is caused by changes in molecular networks, and structure and function after brain injury, leading to a pathological environment that ultimately promotes excitability and produces repeated spontaneous seizures. This process is known as epileptogenesis (Jehi and Vezzani, 2014). The mechanism of epileptogenesis may be multifactorial and is not yet fully understood, limiting the development of new drugs.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain Damage and the Underlying GPR39/ZnT-3 and MBP Expression in the Hippocampus

et al. 2019

View full text Add to dashboard Cite

We previously illustrated that long-term upregulated expression of ZnT-3 in the hippocampus of rats that underwent neonatal seizures was restored by pretreatment with a ketogenic diet. It was recently demonstrated that upregulated expression of ZnT-3 was associated with increased concentrations of intracellular free zinc ions in an in vitro model of glutamate-induced hippocampal neuronal excitotoxic damage. However, there is still a lack of research on the effects of different concentrations of zinc in the diet on developmental convulsive brain injury. The aim of this study was to investigate the effects of different zinc concentrations in the diet on long-term neurobehavioral and seizure thresholds following lithium chloride-pilocarpine-induced developmental seizures. Sprague-Dawley rats (postnatal day 27, P27) were randomly assigned to one of six dietary groups for 4 weeks: normal zinc control group (Control group, 44 mg/kg Zn), Zn-deficient control group (ZD group, 2.7 mg/kg Zn), Zn supplemented control group (ZS group, 246 mg/kg Zn), pilocarpine-induced seizure plus regular zinc diet group (SE group, 44 mg/kg Zn), seizure plus low-zinc diet group (SE + ZD group, 2.7 mg/kg Zn), and seizure plus high-zinc diet group (SE + ZS group, 246 mg/kg Zn). Novel object recognition and passive avoidance tests were performed on rats at P42 and P56. After routine seizure threshold detection and Timm staining procedures at P57, expression of GPR39, ZnT-3, and MBP were detected in the hippocampus by Western blot analysis. The results revealed that the Zinc-deficient diet for 4 weeks aggravated the long-term adverse effects of developmental seizures, evidenced by weight, cognition, seizure threshold and serum zinc concentrations, which were paralleled by expression changes in hippocampal GPR39 and ZnT-3. In contrast, zinc supplementation for 4 weeks significantly improved damage-related changes described above and rescued the abnormal expression of GPR39, ZnT-3, and MBP in the hippocampus. Similar alterations between the expression pattern of MBP and aberrant sprouting of mossy fibers in the hippocampus may indicate that sprouting is a secondary pathological change caused by developmental brain damage rather than the cause of epileptogenesis. Up-regulation of MBP protein levels in the high zinc diet-treated seizure group as well as the corresponding improvement of cognitive impairment and reduced hippocampal mossy fiber regenerative sprouting, may represent a compensatory mechanism for neuronal membrane damage and repair.

show abstract

Novel Concepts in Epileptogenesis and its Prevention

Cited by 9 publications

References 12 publications

Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis

Evaluation of the effects of liraglutide on the development of epilepsy and behavioural alterations in two animal models of epileptogenesis

How to Find Candidate Drug-targets for Antiepileptogenic Therapy?

Long-Term Effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain Damage and the Underlying GPR39/ZnT-3 and MBP Expression in the Hippocampus

Contact Info

Product

Resources

About