Neuronal Degeneration and Neuroprotective Strategies in Epilepsy

Epilepsy is characterised by recurrent seizures that precipitate neuronal injury through repeated bouts of excessive excitatory neurotransmission, metabolic stress and neuroinflammation. In temporal lobe epilepsy, for instance, sustained glutamatergic overactivation induces calcium overload, mitochondrial dysfunction and free‐radical generation, culminating in excitotoxic cell death and hippocampal sclerosis. Concurrent activation of microglia and astrocytes exacerbates synaptic instability and contributes to a maladaptive inflammatory milieu. To address this, contemporary research has focused on neuroprotective strategies that target key pathogenic processes: modulation of glutamate receptors to curb excitotoxicity, attenuation of neuroinflammatory cascades, and preservation of synaptic integrity. Preclinical models of status epilepticus and genetic absence epilepsy have been instrumental in validating candidate interventions. Emerging approaches combine receptor antagonism, anti‐oxidant therapies and modulation of glial responses to prevent seizure‐related degeneration, improve cognitive outcomes and potentially modify disease progression.

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Neuronal Degeneration and Neuroprotective Strategies in Epilepsy publication trend

The graph below shows the total number of articles in neuronal degeneration and neuroprotective strategies in epilepsy across all publications each year (not limited to Nature Index journals).

Technical terms

Excitotoxicity: Neuronal injury or death caused by excessive activation of excitatory amino acid receptors, typically glutamate receptors.

Status epilepticus: A prolonged or rapidly recurring seizure state that can lead to permanent neuronal damage if not promptly controlled.

Reactive gliosis: The activation and proliferation of glial cells (astrocytes and microglia) in response to central nervous system injury or disease.

N-methyl-D-aspartate (NMDA) receptor: A subtype of glutamate receptor permeable to calcium ions, critical for synaptic plasticity but implicated in excitotoxic injury.

Hippocampal sclerosis: A pathological condition characterised by neuronal loss and gliosis in the hippocampus, often associated with refractory temporal lobe epilepsy.

References

1. An In Vivo Electroencephalographic Analysis of the Effect of Riluzole against Limbic and Absence Seizure and Comparison with Glutamate Antagonists. Pharmaceutics (2023).
2. Riluzole attenuates acute neural injury and reactive gliosis, hippocampal-dependent cognitive impairments and spontaneous recurrent generalized seizures in a rat model of temporal lobe epilepsy. Frontiers in Pharmacology (2024).
3. Epileptiform GluN2B–driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy. Experimental Neurology (2022).