Pharmacological perspectives and mechanisms involved in epileptogenesis

Abstract

Background Epileptogenesis can be defined as the process by which a previously healthy brain develops a tendency toward recurrent electrical activity, occurring in three phases: first as an initial trigger (such as stroke, infections, and traumatic brain injury); followed by the latency period and the onset of spontaneous and recurrent seizures which characterizes epilepsy. Main body The mechanisms that may be involved in epileptogenesis are inflammation, neurogenesis, migration of neurons to different regions of the brain, neural reorganization, and neuroplasticity.In recent years, experimental studies have enabled the discovery of several mechanisms involved in the process of epileptogenesis, mainly neuroinflammation, that involves the activation of glial cells and an increase in specific inflammatory mediators. The lack of an experimental animal model protocol for epileptogenic compounds contributes to the difficulty in understanding disease development and the creation of new drugs. Conclusion To solve these difficulties, a new approach is needed in the development of new AEDs that focus on the process of epileptogenesis and the consolidation of animal models for studies of antiepileptogenic compounds, aiming to reach the clinical phases of the study. Some examples of these compounds are rapamycin, which inhibits mTOR signaling, and losartan, that potentiates the antiepileptogenic effect of some AEDs. Based on this, this review discusses the main mechanisms involved in epileptogenesis, as well as its pharmacological approach.

Riluzole and novel naphthalenyl substituted aminothiazole derivatives prevent acute neural excitotoxic injury in a rat model of temporal lobe epilepsy

“…In addition, many of the ASD’s used today have consequential negative side effects such as sedation, mental slowing, and motor reflex reduction ( Walia et al, 2004 ; Perucca and Gilliam, 2012 ; Thigpen et al, 2013 ). A critical goal going forward is to identify new synaptic targets and to develop antiepileptic drugs (AEDs) specific to these targets to prevent acute hippocampal neural injury that can lead to epileptogenesis and epileptic disease, which would be most beneficial in clinical settings ( White and Bialer, 2010 ; Loscher and Schmidt, 2011 ; Kaminski et al, 2014 ; Loscher, 2020 ; Benassi et al, 2021 ; Marques et al, 2022 ).…”