Pathological Targets for Treating Temporal Lobe Epilepsy: Discoveries From Microscale to Macroscale

Abstract

Temporal lobe epilepsy (TLE) is one of the most common and severe types of epilepsy, characterized by intractable, recurrent, and pharmacoresistant seizures. Histopathology of TLE is mostly investigated through observing hippocampal sclerosis (HS) in adults, which provides a robust means to analyze the related histopathological lesions. However, most pathological processes underlying the formation of these lesions remain elusive, as they are difficult to detect and observe. In recent years, significant efforts have been put in elucidating the pathophysiological pathways contributing to TLE epileptogenesis. In this review, we aimed to address the new and unrecognized neuropathological discoveries within the last 5 years, focusing on gene expression (miRNA and DNA methylation), neuronal peptides (neuropeptide Y), cellular metabolism (mitochondria and ion transport), cellular structure (microtubule and extracellular matrix), and tissue-level abnormalities (enlarged amygdala). Herein, we describe a range of biochemical mechanisms and their implication for epileptogenesis. Furthermore, we discuss their potential role as a target for TLE prevention and treatment. This review article summarizes the latest neuropathological discoveries at the molecular, cellular, and tissue levels involving both animal and patient studies, aiming to explore epileptogenesis and highlight new potential targets in the diagnosis and treatment of TLE.

The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

“…1,41 This condition may have devastating consequences [e.g., sudden unexpected death 42 ] and should be taken into account seriously when considering the therapeutic options for the patient. The underlying etiologies of TLE are diverse [2][3][4]43 ; therefore, the treatment plans should differ for different patients (e.g., surgery for lesional TLEs and medical therapy for autoimmune TLEs). Since TLE may be a comorbid condition with SADs, in the current study, we explored whether TLE has shared gene variations with three common SADs (i.e., IDDM, SLE, and RA).…”

“…1 Hippocampal sclerosis (HS), focal cortical dysplasia, tumors, and vascular malformations are important structural etiologies of TLE. 2 However, many patients with TLE may have normal (nonlesional) brain magnetic resonance imaging (MRI). 3 Genetic aberrations, neuroinflammation, and autoimmune processes may play significant roles in the epileptogenesis of TLE, at least in some patients.…”

“…The estimated U.S. prevalence of TLE is 1.9 cases per 1000 people 1 . Hippocampal sclerosis (HS), focal cortical dysplasia, tumors, and vascular malformations are important structural etiologies of TLE 2 . However, many patients with TLE may have normal (nonlesional) brain magnetic resonance imaging (MRI) 3 .…”

An imaging review of the hippocampus and its common pathologies

“…Also known as hippocampal sclerosis, mesial temporal sclerosis is a common cause of medically intractable TLE (56%-70% of cases). 79 It commonly develops after an initial injury following febrile convulsions, CNS infections, or head injuries. In these cases, the use of imaging is not only helpful to reach a diagnosis, but also to determine whether patients are appropriate candidates for temporal lobectomies, which can be curative.…”

Sp1-Mediated Prdx6 Upregulation Leads to Clasmatodendrosis by Increasing Its aiPLA2 Activity in the CA1 Astrocytes in Chronic Epilepsy Rats

“…Temporal lobe epilepsy (TLE) frequently shows poor responses to antiepileptic drugs (AEDs). Aberrant hypersynchronous paroxysmal neuronal discharges in TLE patients lead to further neuronal damage in the various brain regions, especially in the hippocampus (hippocampal sclerosis), which results in secondary symptoms such as cognitive defects and mood disorders [ 1 , 2 ].…”