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Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes
1Department of Neurology, The Third Xiangya Hospital, Central South University Xiangya Medical School, Changsha, China.
Abstract:
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.
Insights
This study optimized a pilocarpine-induced epilepsy model in mice. Using levetiracetam (LEV) to stop seizures significantly increased survival rates, improving animal welfare and research design for mesial temporal lobe epilepsy (mTLE) studies.
Area of Science:
- Neuroscience
- Epilepsy Research
- Animal Models
Background:
- Systemic pilocarpine is used to model mesial temporal lobe epilepsy (mTLE) in rodents.
- Pilocarpine-induced status epilepticus (SE) in mice has a high mortality rate, often due to cardiorespiratory issues.
- Benzodiazepines like diazepam are commonly used to abort SE but are less effective in later stages.
Purpose of the Study:
- To improve the survival rate of pilocarpine-induced SE mouse models.
- To establish a more robust and cost-effective experimental paradigm for mTLE research.
- To investigate the efficacy of levetiracetam (LEV) as an alternative to diazepam for aborting SE.
Main Methods:
- Administered pilocarpine systemically to induce SE in mice.
- Used levetiracetam (LEV), a synaptic vesicle protein 2 (SV2) inhibitor, to abort SE.
- Assessed survival rates and characterized pathological changes in the hippocampus.
Main Results:
- LEV administration significantly increased the survival rate compared to traditional methods.
- Mice developed reliable seizures and characteristic mTLE neuropathology, including neuronal loss and gliosis.
- The optimized protocol provides a more humane and efficient experimental model.
Conclusions:
- Levetiracetam (LEV) is an effective agent for aborting status epilepticus (SE) in pilocarpine-induced mTLE mouse models.
- This optimized protocol enhances animal welfare, reduces research costs, and improves experimental design.
- This approach establishes a reliable mouse model of mTLE with improved survival outcomes.
