Epilepsy, characterized by the occurrence of spontaneous recurrent seizures with CNS origin, presents frequent anti-epileptic drug refractoriness, as occurring in mesial temporal lobe epilepsy (MTLE). As such, the aim of recent therapeutic strategies has shifted from symptomatic seizure control to epileptogenesis prevention. Formerly believed to occur between an initial precipitating brain insult and the first unprovoked epileptic seizure, here referred to as early epileptogenesis, epileptogenesis is now viewed as a continuing process, contributing to the progressive nature of epilepsy long after disease onset. Several cellular mechanisms contribute to early epileptogenesis including altered synaptic plasticity and neuronal excitability, neuronal death, astrocyte dysfunction, neuroinflammation, blood-brain barrier leakage, and aberrant neurogenesis. Targeting these cellular events and establishing the appropriate therapeutic time window for such approaches constitutes a promising strategy to prevent early epileptogenesis as there are to date no proposed treatments in this respect.
New molecular tools to target these early epileptogenic events are also crucial to the development of such strategies. Neuropeptides acting as neurotransmitters, neurotrophic or neuroprotective factors in the central nervous system (CNS), often display anti-inflammatory and neurogenic actions and control epileptogenic phenomena like abnormal synaptic plasticity or brain-barrier leakage and have often been proposed as appealing alternative drug targets in epilepsy, but much remains to be unraveled. Purines, especially adenosine, are for long known to afford neuroprotection in epilepsy, yet current evidence suggests ATP-driven inflammation is involved in the generation of seizures and ATP-gated receptors may contribute to the imbalance in GABA and glutamate release and transport in early epileptogenesis making ATP receptor ligands also appealing drug targets to prevent epileptogenesis. Growing evidence suggests that dysfunctional astrocytes are key players in the early epileptogenesis since astrocytic death occurs soon after status epilepticus, and astrocytes contribute to the generation and spread of seizures and epileptiform activity and the regulation of synaptic plasticity and neuronal excitability at the tripartite synapse. Strategies targeting astrocyte function and survival during and immediately after seizures are thus promising in preventing early epileptogenesis. The neurovascular unit, a group of closely related cells and extracellular matrix components, that englobes neurons, astrocytes, microglia, endothelial cells, pericytes, and smooth muscle cells is also a key player in early epileptogenesis as it is involved in blood-brain barrier leakage and brain immune cell invasion. As such preventing BBB dysfunction may be key to early epileptogenesis prevention.
This Research Topic welcomes submissions of Original Research Articles as well as Hypotheses, Methods, Mini-reviews, and Reviews on new discoveries/approaches to prevent early epileptogenesis that may contribute to the development of new therapeutic strategies covering (but not limited to) the following topics:
• Strategies to prevent pro-epileptogenic synaptic plasticity changes after common epilepsy precipitating events like seizures, ischemia, infection, trauma, etc.
• Approaches to prevent astrocyte contribution to seizure spread and early post-seizure brain damage.
• Discovery and characterization of alternative drug targets (e. g. neuropeptides, ATP) to preventing early post-seizure epileptogenic events.
• Strategies to prevent dysregulation of the neurovascular unit and blood-brain barrier leakage following epileptogenic events.
Epilepsy, characterized by the occurrence of spontaneous recurrent seizures with CNS origin, presents frequent anti-epileptic drug refractoriness, as occurring in mesial temporal lobe epilepsy (MTLE). As such, the aim of recent therapeutic strategies has shifted from symptomatic seizure control to epileptogenesis prevention. Formerly believed to occur between an initial precipitating brain insult and the first unprovoked epileptic seizure, here referred to as early epileptogenesis, epileptogenesis is now viewed as a continuing process, contributing to the progressive nature of epilepsy long after disease onset. Several cellular mechanisms contribute to early epileptogenesis including altered synaptic plasticity and neuronal excitability, neuronal death, astrocyte dysfunction, neuroinflammation, blood-brain barrier leakage, and aberrant neurogenesis. Targeting these cellular events and establishing the appropriate therapeutic time window for such approaches constitutes a promising strategy to prevent early epileptogenesis as there are to date no proposed treatments in this respect.
New molecular tools to target these early epileptogenic events are also crucial to the development of such strategies. Neuropeptides acting as neurotransmitters, neurotrophic or neuroprotective factors in the central nervous system (CNS), often display anti-inflammatory and neurogenic actions and control epileptogenic phenomena like abnormal synaptic plasticity or brain-barrier leakage and have often been proposed as appealing alternative drug targets in epilepsy, but much remains to be unraveled. Purines, especially adenosine, are for long known to afford neuroprotection in epilepsy, yet current evidence suggests ATP-driven inflammation is involved in the generation of seizures and ATP-gated receptors may contribute to the imbalance in GABA and glutamate release and transport in early epileptogenesis making ATP receptor ligands also appealing drug targets to prevent epileptogenesis. Growing evidence suggests that dysfunctional astrocytes are key players in the early epileptogenesis since astrocytic death occurs soon after status epilepticus, and astrocytes contribute to the generation and spread of seizures and epileptiform activity and the regulation of synaptic plasticity and neuronal excitability at the tripartite synapse. Strategies targeting astrocyte function and survival during and immediately after seizures are thus promising in preventing early epileptogenesis. The neurovascular unit, a group of closely related cells and extracellular matrix components, that englobes neurons, astrocytes, microglia, endothelial cells, pericytes, and smooth muscle cells is also a key player in early epileptogenesis as it is involved in blood-brain barrier leakage and brain immune cell invasion. As such preventing BBB dysfunction may be key to early epileptogenesis prevention.
This Research Topic welcomes submissions of Original Research Articles as well as Hypotheses, Methods, Mini-reviews, and Reviews on new discoveries/approaches to prevent early epileptogenesis that may contribute to the development of new therapeutic strategies covering (but not limited to) the following topics:
• Strategies to prevent pro-epileptogenic synaptic plasticity changes after common epilepsy precipitating events like seizures, ischemia, infection, trauma, etc.
• Approaches to prevent astrocyte contribution to seizure spread and early post-seizure brain damage.
• Discovery and characterization of alternative drug targets (e. g. neuropeptides, ATP) to preventing early post-seizure epileptogenic events.
• Strategies to prevent dysregulation of the neurovascular unit and blood-brain barrier leakage following epileptogenic events.
