A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts

Abstract

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.

Targeting brain and peripheral plasticity of the lipidome in acute kainic acid-induced epileptic seizures in mice via quantitative mass spectrometry

“…Although TLE responds well to surgery (80% success rate), post-surgery reoccurrence of seizures remains a concern [2,3]. Multiple possible causes of epilepsy were identified so far, including genetic, physiological, metabolic factors, but about 60% of the epilepsy cases have unknown causes [4][5][6]. In the last decade, the essential role of …”

MicroRNA profiling in the dentate gyrus in epileptic rats

“…However, almost one-third of all patients with epilepsy still have intractable seizures or adverse effects. [6] One compelling challenge for the treatment of epilepsy is to elucidate the molecular mechanisms of disease development and progression.…”

Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis

“…The currently available antiepileptic drugs (AEDs), which act on various molecular targets to reduce the hyperexcitability of neurons, have resulted in great progress in controlling epileptic seizures. Nonetheless, nearly 30% of epilepsy cases are refractory to even the best available AEDs (Amini et al, 2014). Therefore, in addition to neurons, the pathogenesis of epilepsy must be explored in other cell types and structures within the central nervous system (CNS).…”