Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders
Although epilepsy is first known as a disease of seizures and convulsions, most patients with epilepsy also suffer from seizure-associated behavioral abnormalities in motor functions, psychiatric status, and cognition. These neurobehavioral comorbidities may have greater impacts on the quality of li...
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Elsevier
2025-05-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525001613 |
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| author | Chenyao Jiang Ying Yu Jiawang Liu Jianxiong Jiang |
| author_facet | Chenyao Jiang Ying Yu Jiawang Liu Jianxiong Jiang |
| author_sort | Chenyao Jiang |
| collection | DOAJ |
| description | Although epilepsy is first known as a disease of seizures and convulsions, most patients with epilepsy also suffer from seizure-associated behavioral abnormalities in motor functions, psychiatric status, and cognition. These neurobehavioral comorbidities may have greater impacts on the quality of life of people with epilepsy than the seizures themselves and can profoundly interfere with the treatment compliance. While repeated seizures often lead to behavioral comorbidities, certain types of comorbid conditions may potentially increase the risk for epileptic seizures, indicative of some common mechanisms that might underlie these two conditions. As such, emerging evidence supports that inflammation within the brain might represent a key component of such a shared mechanism, given that neuroinflammation can be induced by seizures and various behavioral stressors, and in turn may exacerbate both conditions. Among inflammatory pathways that arise after prolonged seizures, PGE2 signaling via the EP2 receptor promotes cytokine induction, blood–brain barrier disruption, reactive gliosis, neuronal death, and eventually, contributes to behavioral dysfunctions. Pharmacological inhibition of EP2 by small-molecule drug-like antagonists affords broad therapeutic benefits including anti-inflammatory and neuroprotective effects in several rodent seizure models, leading to long-lasting alleviation of neurobehavioral comorbidities, particularly cognitive impairments. Targeting this key inflammatory prostaglandin receptor might provide an adjunctive strategy, along with the current anti-seizure medications, to mitigate cognitive dysfunctions associated with seizure disorders. |
| format | Article |
| id | doaj-art-b634dc8a96b84134a0d1e52e79705df6 |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-b634dc8a96b84134a0d1e52e79705df62025-08-20T03:09:57ZengElsevierActa Pharmaceutica Sinica B2211-38352025-05-011552351236210.1016/j.apsb.2025.03.024Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disordersChenyao Jiang0Ying Yu1Jiawang Liu2Jianxiong Jiang3Department of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, TN 38163, USACorresponding author.; Department of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, TN 38163, USAAlthough epilepsy is first known as a disease of seizures and convulsions, most patients with epilepsy also suffer from seizure-associated behavioral abnormalities in motor functions, psychiatric status, and cognition. These neurobehavioral comorbidities may have greater impacts on the quality of life of people with epilepsy than the seizures themselves and can profoundly interfere with the treatment compliance. While repeated seizures often lead to behavioral comorbidities, certain types of comorbid conditions may potentially increase the risk for epileptic seizures, indicative of some common mechanisms that might underlie these two conditions. As such, emerging evidence supports that inflammation within the brain might represent a key component of such a shared mechanism, given that neuroinflammation can be induced by seizures and various behavioral stressors, and in turn may exacerbate both conditions. Among inflammatory pathways that arise after prolonged seizures, PGE2 signaling via the EP2 receptor promotes cytokine induction, blood–brain barrier disruption, reactive gliosis, neuronal death, and eventually, contributes to behavioral dysfunctions. Pharmacological inhibition of EP2 by small-molecule drug-like antagonists affords broad therapeutic benefits including anti-inflammatory and neuroprotective effects in several rodent seizure models, leading to long-lasting alleviation of neurobehavioral comorbidities, particularly cognitive impairments. Targeting this key inflammatory prostaglandin receptor might provide an adjunctive strategy, along with the current anti-seizure medications, to mitigate cognitive dysfunctions associated with seizure disorders.http://www.sciencedirect.com/science/article/pii/S2211383525001613Behavioral impairmentBlood–brain barrier (BBB)Cognitive deficitCytokineEP2 receptorEpilepsy |
| spellingShingle | Chenyao Jiang Ying Yu Jiawang Liu Jianxiong Jiang Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders Acta Pharmaceutica Sinica B Behavioral impairment Blood–brain barrier (BBB) Cognitive deficit Cytokine EP2 receptor Epilepsy |
| title | Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| title_full | Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| title_fullStr | Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| title_full_unstemmed | Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| title_short | Modulating inflammatory prostaglandin E2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| title_sort | modulating inflammatory prostaglandin e2 signaling to mitigate neurobehavioral comorbidities associated with seizure disorders |
| topic | Behavioral impairment Blood–brain barrier (BBB) Cognitive deficit Cytokine EP2 receptor Epilepsy |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525001613 |
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