BRIEF RESEARCH REPORT article
Front. Neurosci.
Sec. Neuroscience Methods and Techniques
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1592014
Refinement of the Pilocarpine-Induced Status Epilepticus Model in Mice to Improve Mortality Outcomes
Provisionally accepted
- 1Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- 2University of Michigan, Ann Arbor, Michigan, United States
- 3Ann Arbor VA Hospital, Ann Arbor, MI, 48109, Ann Arbor, United States
- 4Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, Ann Arbor, United States
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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.
Keywords: levetiracetam, Pilocarpine, Status Epilepticus, Mortality rate, Mesial temporal lobe epilepsy
Received: 11 Mar 2025; Accepted: 18 Apr 2025.
Copyright: © 2025 Jiang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yu Wang, University of Michigan, Ann Arbor, 48109, Michigan, United States
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