Viral Infections and Neuroinflammation in Epilepsy

Viral infections of the central nervous system represent a significant trigger for both acute seizures and the later development of epilepsy. Neuroinflammation, driven by activation of resident glial cells and infiltration of peripheral immune cells, underlies neuronal hyperexcitability and network reorganisation. Disruption of the blood–brain barrier facilitates entry of cytokines and chemokines into the parenchyma, where microglia and astrocytes release mediators such as tumour necrosis factor-α and interleukin-1β. These factors alter synaptic composition, modulate glutamatergic and GABAergic transmission, and can promote neuronal death or aberrant circuit formation. Clinical manifestations range from transient, infection-related seizures to chronic, drug-resistant epilepsy. Advances in neuroimaging, molecular biomarkers and animal models have clarified the interplay between viral tropism, immune response and epileptogenesis. A growing emphasis on anti-inflammatory and neuroprotective strategies offers opportunities for targeted intervention, with the ultimate aim of preventing seizure recurrence and preserving cognitive function in affected individuals worldwide.

Research from Nature Portfolio

Recent studies have refined the experimental toolkit for investigating virus-induced epilepsy without compromising research validity. In a refined encephalitis model, perioperative administration of a non-steroidal anti-inflammatory agent was shown to alleviate procedural discomfort in mice without altering seizure burden, hippocampal inflammation or neurodegeneration, thus supporting improved animal welfare alongside robust data collection. Foundational work has also demonstrated that inhibition of calpain, a protease activated during acute viral encephalitis, protects hippocampal neurons and preserves learning and memory in mouse models, while significantly attenuating escalation of seizure activity. These findings underscore the potential of adjunct therapies that mitigate inflammation-driven neuronal injury in the context of central nervous system viral infection.

Viral Infections and Neuroinflammation in Epilepsy publication trend

The graph below shows the total number of articles in viral infections and neuroinflammation in epilepsy across all publications each year (not limited to Nature Index journals).

Technical terms

Neuroinflammation: Inflammatory response within the central nervous system involving glial activation and cytokine release.

Blood–brain barrier (BBB): Selective permeability barrier between the circulating blood and brain tissue.

Microglia: Resident immune cells of the central nervous system that mediate inflammatory responses.

Chemokine: Small signalling protein that directs the migration of immune cells to sites of inflammation.

Epileptogenesis: Process by which a normal brain develops a predisposition to recurrent seizures following an insult.

Ictogenesis: Initiation phase of seizure activity in the brain.

References

1. Testing perioperative meloxicam analgesia to enhance welfare while preserving model validity in an inflammation-induced seizure model. Scientific Reports (2024).
2. Neuroprotection mediated by inhibition of calpain during acute viral encephalitis. Scientific Reports (2016).
3. Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment. International Journal of Molecular Sciences (2024).
4. Molecular Mechanisms in the Genesis of Seizures and Epilepsy Associated With Viral Infection. Frontiers in Molecular Neuroscience (2022).
5. Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, modifies acute seizure burden and chronic epilepsy-related behavioral deficits following Theiler's virus infection in mice. Neuropharmacology (2022).