Mechanisms of Epileptogenesis

Avanzini, G.; Franceschetti, Silvana

doi:10.1002/9781444316667.ch5

Cited by 9 publications

(10 citation statements)

References 97 publications

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“…Beyond instigating abnormal activity within individual neurons, alterations in excitability, intrinsic to epileptogenesis, encompass networks of hyperexcitable cells. These cells function cohesively, demonstrating a high degree of coordination via both functional and potentially dysfunctional pathways [39].…”

Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

“…This mechanism forms the basis of the intrinsic electrical impulse observed in layer V pyramidal neurons. Consequently, this inherent electrical discharge extends throughout axon branches, fostering synaptic connections with proximate neurons and preserving their synchronized activity [39].…”

Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

“…Conversely, anion channels are instrumental in executing inhibitory processes that counteract neuronal stimulation. Disturbances in ion charge equilibrium resulting from anomalies in anion or cation channel function, known as channelopathies, have the potential to trigger epileptogenesis [4,39,40].…”

Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

“…Firstly, it can trigger paroxysmal depolarizing shifts (PDS) inducing electrical bursts within the affected neurons. Secondly, it can enhance synchronization stemming from intrinsic electrical bursts in the pyramidal neurons of the neocortex's layer V. As a consequence, a substantial cohort of neurons becomes engaged, thereby laying the foundation for an epileptogenic process to take root [39,40].…”

Section: Sodium Ion Channelsmentioning

confidence: 99%

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Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Sumadewi,

Harkitasari,

Tjandra

2023

Acta Epileptologica

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Epilepsy is a recurring neurological disease caused by the abnormal electrical activity in the brain. This disease has caused about 50 new cases in 100,000 populations every year with the clinical manifestations of awareness loss, bruising, and mobility abnormalities. Due to the lack understanding of the pathophysiology behind the illness, a wide variety of medications are available to treat epilepsy. Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. This is related to the inflammation which is driven by cytokines like IL-1 and tumor necrosis factor-α (TNF-α) leads to neuronal hyperexcitability. Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. The blood-brain barrier (BBB) maintains central nervous system integrity through its tight endothelial connections, but inflammation impact BBB structure and function which leads to immune cell infiltration. The mammalian target of rapamycin (mTOR) pathway’s excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. Thalamocortical circuitry disruption is central to absence epilepsy, the normal circuit becomes faulty and results in characteristic brain wave patterns.

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Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

Section: Ionic Environment Modifications Causing Epileptic Seizures A...mentioning

confidence: 99%

Section: Sodium Ion Channelsmentioning

confidence: 99%

See 2 more Smart Citations

Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Sumadewi,

Harkitasari,

Tjandra

2023

Acta Epileptologica

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“…Epileptogenesis is a process when the brain under normal conditions undergoes functional changes in the form of abnormal electrical activity, resulting in chronic seizures. In general, epileptogenesis consists of three stages, namely acute events or precipitating events, latent or clinically silent periods, and stages of chronic epilepsy or spontaneous seizures [ 59 – 61 ]. Trigger factors can be in the form of oxidation, inflammation, neurogenesis, apoptosis, and synaptic plasticity.…”

Section: Anti-hmgb1 Monoclonal Antibody In Epilepsymentioning

confidence: 99%

Anti-high mobility group box protein 1 monoclonal antibody downregulating P-glycoprotein as novel epilepsy therapeutics

Liyis

Tandy

Endira

et al. 2022

Egypt J Neurol Psychiatry Neurosurg

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Epilepsy, a neurological illness, is characterized by recurrent uncontrolled seizures. There are many treatments of options that can be used as the therapy of epilepsy. However, anti-seizure medications as the primary treatment choice for epilepsy show many possible adverse effects and even pharmacoresistance to the therapy. High Mobility Group Box 1 (HMGB1) as an initiator and amplifier of the neuroinflammation is responsible for the onset and progression of epilepsy by overexpressing P-glycoprotein on the blood brain barrier. HMGB1 proteins then activate TLR4 in neurons and astrocytes, in which proinflammatory cytokines are produced. Anti-HMGB1 mAb works by blocking the HMGB1, reducing inflammatory activity in the brain that may affect epileptogenesis. Through the process, anti-HMGB1 mAb reduces the TLR4 activity and other receptors that may involve in promote signal of epilepsy such as RAGE. Several studies have shown that anti-HMGB1 has the potential to inhibit the increase in serum HMGB1 in plasma and brain tissue. Further research is needed to identify the mechanism of the inhibiting of overexpression of P-glycoprotein through anti-HMGB1 mAb.

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Mechanisms of Epileptogenesis

Cited by 9 publications

References 97 publications

Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Anti-high mobility group box protein 1 monoclonal antibody downregulating P-glycoprotein as novel epilepsy therapeutics

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