Targeting Inflammation in the Treatment of Post-Stroke Epileptogenesis

Benjamin Moore^*
*Correspondence: Benjamin Moore, Department of Neurology, University of Sydney, Sydney, Australia, Email:

Introduction

Post-Stroke Epilepsy (PSE) represents a significant neurological complication following ischemic stroke, characterized by recurrent seizures that can severely impact a patientâ??s quality of life. Emerging research has identified inflammation as a critical driver of epileptogenesis the process by which a normal brain develops epilepsy particularly in the context of ischemic brain injury. Stroke-induced neuronal damage triggers a cascade of inflammatory responses, including the release of pro-inflammatory cytokines, activation of microglia and infiltration of immune cells, which collectively contribute to hyperexcitability and seizure susceptibility. This understanding has shifted the therapeutic focus toward targeting inflammation to prevent or mitigate PSE, offering hope for novel interventions that address the root causes of epileptogenesis rather than merely controlling seizures. By exploring the interplay between inflammation and epileptogenesis, this article aims to highlight the potential of anti-inflammatory strategies in transforming the management of post-stroke epilepsy [1].

Description

The inflammatory response following an ischemic stroke is a complex and dynamic process that plays a dual role in brain repair and pathology. Immediately after a stroke, damaged neurons and glial cells release Danger-Associated Molecular Patterns (DAMPs), which activate resident immune cells like microglia and astrocytes. These cells produce pro-inflammatory mediators such as Inter Leukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α) and Inter Leukin-6 (IL-6), creating an inflammatory microenvironment that disrupts the blood-brain barrier and recruits peripheral immune cells. This heightened inflammatory state alters neuronal excitability by modulating ion channels, neurotransmitter receptors and synaptic plasticity, laying the groundwork for epileptogenesis. For instance, IL-1β has been shown to enhance glutamatergic transmission and reduce GABAergic inhibition, promoting hyperexcitability in the post-stroke brain. Additionally, chronic inflammation can lead to persistent gliosis and neuronal circuit remodeling, further increasing seizure risk. Studies, such as those by Tröscher et al. (2021), have demonstrated that inflammation-mediated pathways are central to ischemic post-stroke epilepsy, suggesting that targeting these processes could interrupt epileptogenic progression. Experimental models have revealed that inhibiting specific inflammatory pathways, such as the IL-1β signaling cascade, reduces seizure frequency and severity, underscoring the therapeutic promise of anti-inflammatory interventions.

Building on this mechanistic insight, several anti-inflammatory strategies are being explored for the prevention and treatment of PSE. Pharmacological agents, such as IL-1 receptor antagonists (e.g., anakinra) and TNF-α inhibitors, have shown efficacy in preclinical models by attenuating neuroinflammation and reducing seizure susceptibility. Additionally, drugs targeting microglial activation, such as minocycline, have demonstrated potential in modulating the inflammatory response and protecting against epileptogenesis. Beyond traditional pharmaceuticals, emerging therapies like monoclonal antibodies and gene therapies aim to precisely target inflammatory mediators, offering greater specificity and fewer off-target effects. Non-pharmacological approaches, including ketogenic diets and vagus nerve stimulation, have also been investigated for their anti-inflammatory properties, with preliminary evidence suggesting they may reduce seizure risk in post-stroke patients. However, translating these findings into clinical practice remains challenging due to the heterogeneity of stroke patients, variability in inflammatory responses and the need for timely intervention to prevent irreversible epileptogenic changes. Clinical trials are underway to evaluate the safety and efficacy of anti-inflammatory treatments in PSE, with a focus on identifying biomarkers such as elevated cytokine levels or neuroimaging signatures of inflammation that could guide personalized therapy. These advancements highlight the potential of inflammation-targeted treatments to not only manage seizures but also prevent the onset of epilepsy in at-risk stroke survivors [2].

Conclusion

Targeting inflammation offers a promising avenue for the treatment and prevention of post-stroke epileptogenesis, addressing a critical gap in the management of post-stroke epilepsy. By interrupting the inflammatory cascades that drive neuronal hyperexcitability and circuit remodeling, anti-inflammatory therapies have the potential to reduce seizure risk and improve long-term outcomes for stroke survivors. While preclinical studies have provided robust evidence for the role of inflammation in PSE, ongoing clinical research is essential to translate these findings into effective, patient-specific treatments. The integration of biomarkers, advanced therapeutics and non-pharmacological interventions could pave the way for a new era in PSE management, where the focus shifts from symptom control to disease modification. As our understanding of the inflammatory mechanisms underlying epileptogenesis deepens, so too does the hope for innovative strategies that enhance recovery and quality of life for those affected by post-stroke epilepsy.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Zelano, Johan, Martin Holtkamp, Nivedita Agarwal and Simona Lattanzi, et al. "How to diagnose and treat post�stroke seizures and epilepsy." Epileptic Disord 22 (2020): 252-263.

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2. Tröscher, Anna Regina, Joachim Gruber, Judith N. Wagner and Vincent Böhm, et al. "Inflammation mediated epileptogenesis as possible mechanism underlying ischemic post-stroke epilepsy." Front Aging Neurosci 13 (2021): 781174.

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