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The potential role of COX-2/PGs signaling pathway in epileptogenesis and associated neuroinflammation: collusions or serendipity.

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Title: The potential role of COX-2/PGs signaling pathway in epileptogenesis and associated neuroinflammation: collusions or serendipity.
Authors: Alsfouk, Bshra A. (AUTHOR), Al-Kuraishy, Hayder M. (AUTHOR), Al-Gareeb, Ali I. (AUTHOR), Abdelaziz, Ahmed M. (AUTHOR), Ismail, Alaa (AUTHOR), Alkazmi, Luay M. (AUTHOR), Alexiou, Athanasios (AUTHOR), Papadakis, Marios (AUTHOR), El-Saber Batiha, Gaber (AUTHOR)
Source: Neurological Sciences. Feb2026, Vol. 47 Issue 2, p1-18. 18p.
Abstract: Background: Epilepsy is a neurological condition characterized by recurrent, spontaneous seizures stemming from sudden, abnormal synchronization of neuronal activity in specific brain regions, driven by structural or functional alterations. This disorder is preceded by epileptogenesis, a dynamic process marked by cellular and molecular changes that heighten brain excitability. Although anti-seizure medications (ASMs) remain the cornerstone of treatment, roughly 30% of patients develop refractory epilepsy, which resists ASMs therapy. Critically, ASMs do not prevent epileptogenesis, implying divergent mechanisms govern disease progression. Methods: This review evaluates the pathway’s contributions to neuroinflammation, epileptogenesis, and epilepsy, and explores the promise of COX-2 inhibitors in managing refractory epilepsy. Results: Epileptogenesis continues even after seizures manifest and is strongly associated with drug-resistant forms such as temporal lobe epilepsy (TLE). Neuroinflammation, which develops subsequent to the epileptic seizure, aggravates refractory epilepsy by enhancing the extrusion of ASMs across the blood-brain barrier (BBB), reducing their therapeutic efficacy. Following epileptic seizures, cyclooxygenase-2 (COX-2), a key enzyme in prostaglandin (PG) synthesis, is upregulated and activates the COX-2/PG pathway, leading to exacerbation of neuroinflammation and acceleration of epilepsy progression. Furthermore, by inducing neuronal hyperexcitability and epileptogenesis, elevated COX-2 and PG levels correlate with increased seizure severity and frequency. Conclusion: Consequently, targeting of the COX-2/PG axis has emerged as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
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Abstract:Background: Epilepsy is a neurological condition characterized by recurrent, spontaneous seizures stemming from sudden, abnormal synchronization of neuronal activity in specific brain regions, driven by structural or functional alterations. This disorder is preceded by epileptogenesis, a dynamic process marked by cellular and molecular changes that heighten brain excitability. Although anti-seizure medications (ASMs) remain the cornerstone of treatment, roughly 30% of patients develop refractory epilepsy, which resists ASMs therapy. Critically, ASMs do not prevent epileptogenesis, implying divergent mechanisms govern disease progression. Methods: This review evaluates the pathway’s contributions to neuroinflammation, epileptogenesis, and epilepsy, and explores the promise of COX-2 inhibitors in managing refractory epilepsy. Results: Epileptogenesis continues even after seizures manifest and is strongly associated with drug-resistant forms such as temporal lobe epilepsy (TLE). Neuroinflammation, which develops subsequent to the epileptic seizure, aggravates refractory epilepsy by enhancing the extrusion of ASMs across the blood-brain barrier (BBB), reducing their therapeutic efficacy. Following epileptic seizures, cyclooxygenase-2 (COX-2), a key enzyme in prostaglandin (PG) synthesis, is upregulated and activates the COX-2/PG pathway, leading to exacerbation of neuroinflammation and acceleration of epilepsy progression. Furthermore, by inducing neuronal hyperexcitability and epileptogenesis, elevated COX-2 and PG levels correlate with increased seizure severity and frequency. Conclusion: Consequently, targeting of the COX-2/PG axis has emerged as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]
ISSN:15901874
DOI:10.1007/s10072-025-08679-6