MECHANISMS BEHIND EPILEPTOGENESIS: A COMPREHENSIVE REVIEW
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Abstract
Epilepsy is defined as a chronic disorder of the nervous system with an aberration of unprovoked seizures that happen due to abnormal bursts of electrical activity in the brain. The process of transitioning from a normal brain to an epileptic one, known as epileptogenesis, is both of great complexity and multifactorial. It encompasses changes in neurobiology that foster abnormal brain excitability within the brain and disrupt homeostasis of excitation and inhibition of the brain’s neurotransmitters. Although the process of epileptogenesis has not been fully elucidated, there is evidence to suggest that multiple cellular and molecular changes within the brain are of critical importance. In this review, we focus on the mechanisms of epileptogenesis, which include plastic changes, ion channel dysfunctions, GABAergic failure, inflammation, and neurogenesis, highlighting their relative interplay within the epileptogenic focus.
Recent advances in precision medicine and epigenetic mechanisms have revealed quantitative biomarker profiles, with neuroinflammatory cytokines showing progressive elevation from healthy controls (TNF-α <8.1 pg/ml) to drug-resistant epilepsy (TNF-α 28.4-78.9 pg/ml), while ion channel mutations demonstrate specific prevalence patterns with SCN1A mutations affecting 2.5 per 100,000 individuals.
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