Biomolecular mechanisms of epileptic seizures and epilepsy: a review

Abstract

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.

Serum Leptin levels in newly diagnosed Epileptic Patients

“…Leptin has been identified as a neuroprotective agent 9 . The present study reported serum leptin levels of adolescent (12)(13)(14)(15)(16)(17)(18)(19) and young adults (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) adults who were newly-diagnosed and treatment-naive epileptic patients, and compared the levels with those of healthy individuals. To our knowledge, the current study is the first of its kind.…”

“…On the global scale, epilepsy is the 5th most prevalent neurological disorder, following stroke, migraine, dementia and meningitis 4 . Epileptogenesis refers to the exaggerated transformation of a typically functioning brain, resulting in the onset of epilepsy 14 . This process induces molecular modifications in the hippocampus, including changes in neurogenesis and heightened levels of neurotrophic factors and proteins.…”

“…This process induces molecular modifications in the hippocampus, including changes in neurogenesis and heightened levels of neurotrophic factors and proteins. 14 Leptin is a neurotropic factor, and it contributes to the growth, maturation and viability of neurons within the brain. Leptin receptors are expressed in widespread regions of the brain, such as the hippocampus, hypothalamus and cortex 15 .…”

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…Beyond neurotransmitter signaling, imbalances in other neurotransmitter systems, such as serotonin, dopamine, and acetylcholine, are implicated in epilepsy pathophysiology [ 94 ]. Additionally, alterations in proteins regulating neuronal excitability and synaptic plasticity, including neurotransmitter receptors and ion channels, further influence seizure susceptibility [ 91 , 95 ]. Moreover, neuroinflammation, characterized by the activation of microglia and the release of pro-inflammatory cytokines, can alter neuronal excitability and contribute to seizure progression [ 96 ].…”

Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

“…Convulsions emerge due to an imbalance between excitatory and inhibitory systems within the central nervous system. Based on distinct electrophysiological and clinical characteristics, seizures have recently been categorized into focal and generalized convulsive, as well as non-convulsive epilepsies [3][4].…”