A Molecular Approach to Epilepsy Management; from Current Therapeutic Methods to Preconditioning Efforts
Molecular Neurobiology, 1-22. DOI: 10.1007/s12035-014-8876-5
53 Pages Posted: 1 Dec 2014
Date Written: September 9, 2014
Epilepsy is a 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 evidence declare that microglia and astrocytes activations, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABA-ergic 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 pathogenesis of epilepsy, and discuss recent therapeutic strategies in treatments of epilepsy. We will highlight that novel therapy targeting such as preconditioning process hold great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
Keywords: Epilepsy, seizure, inflammation, neuroprotection, tolerance, oxidative stress, mitochondria dysfunction, apoptosis, preconditioning
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