Abstract
Translational large-animal models that can accommodate human-scale implantable devices are essential for advancing neuromodulation therapies in epilepsy. This study establishes a kainic acid (KA)-induced porcine model of mesial temporal lobe epilepsy (mTLE) using clinical imaging, stereotactic surgery, and a fully implantable neural stimulator-recorder (INSR) device designed for humans. Seven pigs (six KA-treated and one saline control) underwent MRI-guided stereotactic implantation of electrodes targeting bilateral hippocampus (HPC) and anterior thalamus (ANT), followed by intra-hippocampal KA or saline infusion. Local field potentials (LFP) were recorded continuously with synchronized video monitoring. Seizures and LFP interictal epileptiform-like discharges (IEDs) were quantified using validated automated detectors. Histology was performed in the saline control and the longest surviving KA-treated pig. Intra-hippocampal KA infusion induced acute status epilepticus in all treated pigs (6/6). Four animals survived to chronic monitoring with spontaneous seizures observed in three pigs (2,733 seizures; mean duration of 27.2 ± 17.6 s). IEDs were observed in bilateral HPC of all animals, including saline control, with higher rates in the lesioned HPC (p < 0.0001). While the IED morphology is consistent with epileptiform activity, IEDs alone are not specific for epilepsy and physiological transients (e.g. sharp-wave ripples) and injury-related hyperexcitability or strain-specific hyperexcitability cannot be excluded. Histological analysis revealed patchy neuronal loss and cytoarchitectural changes in HPC. This porcine model reproduces electrophysiological features of human mTLE. This approach provides a powerful translational bridge for developing and testing next-generation INSR and neuromodulation strategies in freely behaving large animals.
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Abbreviations
- ANT:
-
Anterior nucleus of thalamus
- AUC:
-
Area under the curve
- CT:
-
Computed tomography
- CV:
-
Cresyl violet
- DBS:
-
Deep brain stimulation
- DG:
-
Dentate gyrus
- FBTCS:
-
Focal to bilateral tonic-clonic seizures
- FGATIR:
-
Fast gray matter acquisition T1 inversion recovery
- HFO:
-
High frequency oscillations
- HPC:
-
Hippocampus
- ICC:
-
Intraclass correlation coefficient
- IEDs:
-
Interictal epileptiform-like discharges
- INSR:
-
Implantable Neural Stimulator-Recorder
- KA:
-
Kainic acid
- LFP:
-
Local field potential
- MPRAGE:
-
Magnetization-prepared rapid gradient echo
- MRI:
-
Magnetic resonance imaging
- mTLE:
-
Mesial temporal lobe epilepsy
- MTT:
-
Mammillothalamic tract
- PPV:
-
Positive predictive value
- SE:
-
Status epilepticus
- SPEP:
-
Single pulse evoked potentials
Acknowledgements
Cadence Neuroscience Inc. provided the workstation and implantable hardware. We thank the XRI Core and Department of Comparative Medicine within Mayo Clinic for supporting our experiments. We thank Certicon a.s. for providing CyberPSG and to Wavesurfers s.r.o. for providing EEG Wave that enabled us to review and analyze our data. Figure drawings were made by the manuscript authors. The renderings of the workstation and implantable systems were provided by Cadence Neuroscience.
Funding
This research was supported by NIH R01-NS092882. Cadence Neuroscience provided the devices.
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Competing interests
G.A.W. and J.V.G have licensed intellectual property developed at Mayo Clinic to Cadence Neuroscience and to NeuroOne Inc. Mayo Clinic has received research support and consulting fees on behalf of G.A.W. from Cadence Neuroscience, NeuroOne, and Medtronic. F.M. received a salary support from Cadence Neuroscience Inc.
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Mivalt, F., Maltais, D., Kim, I. et al. Kainic acid pig model of hippocampal epilepsy. Sci Rep (2026). https://doi.org/10.1038/s41598-026-55135-2
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DOI: https://doi.org/10.1038/s41598-026-55135-2
