Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes
Systemic pilocarpine administration has been widely implemented to generate rodent models of mesial temporal lobe epilepsy (mTLE), but pilocarpine-induced status epilepticus (SE) in mice causes a high mortality rate, likely due to cardiorespiratory collapse associated with prolonged seizures. Althou...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1592014/full |
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| author | Mi Jiang Mi Jiang Yu Wang Yu Wang Yu Wang |
| author_facet | Mi Jiang Mi Jiang Yu Wang Yu Wang Yu Wang |
| author_sort | Mi Jiang |
| collection | DOAJ |
| description | Systemic pilocarpine administration has been widely implemented to generate rodent models of mesial temporal lobe epilepsy (mTLE), but pilocarpine-induced status epilepticus (SE) in mice causes a high mortality rate, likely due to cardiorespiratory collapse associated with prolonged seizures. Although it has been well known that SE impairs the functional properties of GABARs and benzodiazepine is not effective in treating late SE both in humans and experimental animals, diazepam is still the most commonly used medication to abort SE in pilocarpine-mTLE models. Here, we instead used levetiracetam (LEV), a specific synaptic vesicle protein 2 (SV2) inhibitor in presynaptic terminals, to abort SE and achieved a substantially increased survival rate, providing a robust experimental paradigm to improve animal welfare, research cost, and experimental design. Comparable to previous studies, these mice developed reliable seizures and pathological changes in the hippocampus, including neuronal loss, gliosis, and mossy fiber sprouting. In summary, our optimized LEV-treated, pilocarpine-based protocol establishes a reliable mouse model of mTLE with significantly improved survival outcomes. |
| format | Article |
| id | doaj-art-c0b2ffae592f4e6085124f30dbd528a2 |
| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-c0b2ffae592f4e6085124f30dbd528a22025-08-20T02:14:19ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-05-011910.3389/fnins.2025.15920141592014Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomesMi Jiang0Mi Jiang1Yu Wang2Yu Wang3Yu Wang4Department of Neurology, The Third Xiangya Hospital, Central South University Xiangya Medical School, Changsha, ChinaDepartment of Neurology, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurology, University of Michigan, Ann Arbor, MI, United StatesAnn Arbor VA Hospital, Ann Arbor, MI, United StatesNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United StatesSystemic pilocarpine administration has been widely implemented to generate rodent models of mesial temporal lobe epilepsy (mTLE), but pilocarpine-induced status epilepticus (SE) in mice causes a high mortality rate, likely due to cardiorespiratory collapse associated with prolonged seizures. Although it has been well known that SE impairs the functional properties of GABARs and benzodiazepine is not effective in treating late SE both in humans and experimental animals, diazepam is still the most commonly used medication to abort SE in pilocarpine-mTLE models. Here, we instead used levetiracetam (LEV), a specific synaptic vesicle protein 2 (SV2) inhibitor in presynaptic terminals, to abort SE and achieved a substantially increased survival rate, providing a robust experimental paradigm to improve animal welfare, research cost, and experimental design. Comparable to previous studies, these mice developed reliable seizures and pathological changes in the hippocampus, including neuronal loss, gliosis, and mossy fiber sprouting. In summary, our optimized LEV-treated, pilocarpine-based protocol establishes a reliable mouse model of mTLE with significantly improved survival outcomes.https://www.frontiersin.org/articles/10.3389/fnins.2025.1592014/fulllevetiracetampilocarpinestatus epilepticusmortality ratemesial temporal lobe epilepsy |
| spellingShingle | Mi Jiang Mi Jiang Yu Wang Yu Wang Yu Wang Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes Frontiers in Neuroscience levetiracetam pilocarpine status epilepticus mortality rate mesial temporal lobe epilepsy |
| title | Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes |
| title_full | Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes |
| title_fullStr | Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes |
| title_full_unstemmed | Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes |
| title_short | Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes |
| title_sort | refinement of the pilocarpine induced status epilepticus model in mice to improve mortality outcomes |
| topic | levetiracetam pilocarpine status epilepticus mortality rate mesial temporal lobe epilepsy |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1592014/full |
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