Biomolecular mechanisms of epileptic seizures and epilepsy: a review  

作　　者：Komang Trisna Sumadewi Saktivi Harkitasari David Christopher Tjandra 

机构地区：[1]Anatomy-Histology Department,Faculty of Medicine and Health Science,Warmadewa University,Denpasar,80235,Indonesia [2]Neurology Department,Faculty of Medicine and Health Science,Warmadewa University,Denpasar,80235,Indonesia [3]Bachelor of Medicine Study Program,Faculty of Medicine,Udayana University,Denpasar,80234,Indonesia

出　　处：《Acta Epileptologica》2023年第4期201-222,共22页癫痫学报（英文）

摘　　要：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

关 键 词：Epilectic seizures EPILEPSY EPILEPTOGENESIS Molecular mechanism 

分 类 号：R742.1[医药卫生—神经病学与精神病学]