| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Yasmen, Nelufar Sluter, Madison N. Li, Lexiao Yu, Ying Jiang, Jianxiong |
| Abstract | Status epilepticus (SE) in humans is characterized by prolonged convulsive seizures that are generalized and often difficult to control. The current antiseizure drugs (ASDs) aim to stop seizures quickly enough to prevent the SE-induced brain inflammation, injury, and long-term sequelae. However, sole reliance on acute therapies is imprudent because prompt treatment may not always be possible under certain circumstances. The pathophysiological mechanisms underlying the devastating consequences of SE are presumably associated with neuroinflammatory reactions, where prostaglandin E2 (PGE2) plays a pivotal role. As the terminal synthase for pathogenic PGE2, the microsomal prostaglandin E synthase-1 (mPGES-1) is rapidly and robustly induced by prolonged seizures. Congenital deletion of mPGES-1 in mice is neuroprotective and blunts gliosis following chemoconvulsant seizures, suggesting the feasibility of mPGES-1 as a potential antiepileptic target. Herein, we investigated the effects of a dual species mPGES-1 inhibitor in a mouse pilocarpine model of SE. Treatment with the mPGES-1 inhibitor in mice after SE that was terminated by diazepam, a fast-acting benzodiazepine, time-dependently abolished the SE-induced PGE2 within the brain. Its negligible effects on cyclooxygenases, the enzymes responsible for the initial step of PGE2 biosynthesis, validated its specificity to mPGES-1. Post-SE inhibition of mPGES-1 also blunted proinflammatory cytokines and reactive gliosis in the hippocampus and broadly prevented neuronal damage in a number of brain areas. Thus, pharmacological inhibition of mPGES-1 by small-molecule inhibitors might provide an adjunctive strategy that can be implemented hours after SE, together with first-line ASDs, to reduce SE-provoked brain inflammation and injury. |
| Related Links | https://molecularbrain.biomedcentral.com/counter/pdf/10.1186/s13041-023-01008-y.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17566606 |
| DOI | 10.1186/s13041-023-01008-y |
| Journal | Molecular Brain |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2023-01-25 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Psychopharmacology Antiseizure drugs (ASDs) Epilepsy Epileptogenesis Reactive gliosis Inhibitor Microsomal prostaglandin E synthase-1 (mPGES-1) Neuroinflammation Neuroprotection Prostaglandin E2 (PGE2) Seizures |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cellular and Molecular Neuroscience Molecular Biology |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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