Astrocyte Role in Temporal Lobe Epilepsy and Development of Mossy Fiber Sprouting

Abstract

Epilepsy affects approximately 50 million people worldwide, with 60% of adult epilepsies presenting an onset of focal origin. The most common focal epilepsy is temporal lobe epilepsy (TLE). The role of astrocytes in the presentation and development of TLE has been increasingly studied and discussed within the literature. The most common histopathological diagnosis of TLE is hippocampal sclerosis. Hippocampal sclerosis is characterized by neuronal cell loss within the Cornu ammonis and reactive astrogliosis. In some cases, mossy fiber sprouting may be observed. Mossy fiber sprouting has been controversial in its contribution to epileptogenesis in TLE patients, and the mechanisms surrounding the phenomenon have yet to be elucidated. Several studies have reported that mossy fiber sprouting has an almost certain co-existence with reactive astrogliosis within the hippocampus under epileptic conditions. Astrocytes are known to play an important role in the survival and axonal outgrowth of central and peripheral nervous system neurons, pointing to a potential role of astrocytes in TLE and associated cellular alterations. Herein, we review the recent developments surrounding the role of astrocytes in the pathogenic process of TLE and mossy fiber sprouting, with a focus on proposed signaling pathways and cellular mechanisms, histological observations, and clinical correlations in human patients.

The Interconnected Mechanisms of Oxidative Stress and Neuroinflammation in Epilepsy

“…For example, a key aspect of glutamate physiology associated with epilepsy and OS is the neuron-astrocyte interaction. Astrocytes are responsible for the uptake of glutamate from the synaptic cleft, and in temporal lobe epilepsy (TLE), astrocyte-mediated glutamate clearance via the astrocytic glutamate transporter (GLT-1) is defective, resulting in glutamate accumulation and excitotoxicity [ 94 , 95 ]. Other well-studied and important contributions of astrocytes to synaptic dysfunction in epilepsy are astrocyte-mediated impaired potassium (K + ) buffering, aquaporin (AQP4) dysfunction and excessive astroglial ATP release and purine receptor activation (reviewed in [ 93 ]).…”

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy

“…The functional role of GFAP in astrocytes has been widely accepted, which is involved in the process of regeneration, synaptic remodeling, and reactive gliosis [ 37 , 38 ]. Hippocampal sclerosis is the most common feature in TLE, which is due to the proliferation and hypertrophy of astrocytes resulted from increased glia-associated proteins [ 39 , 40 ]. An increased GFAP and typical gliosis have been observed within the hippocampus in our present research, which further consolidate the insight that increased GFAP is involved in hippocampal gliosis and epileptogenesis.…”

Astrocytes as a target for therapeutic strategies in epilepsy: current insights

“…According to these studies, astrocyte dysfunction contributes to neuronal hyperexcitation, neurotoxicity, and epileptogenesis, or the seizure spread ( Steinhäuser et al, 2012 ). Reactive astrogliosis in response to the initial insult, is frequently prominent and almost always coexists with hippocampal sclerosis, which is the most common histopathological finding in TLE ( Twible et al, 2021 ). Proposed mechanisms of astrocyte involvement in structural/metabolic/infectious/immune epilepsy particularly in TLE will be summarized below.…”