Authors :
Presenting Author: Leonardo Silenieks, MSc – Transpharmation Inc.
Annette Pisanski, PhD – Transpharmation Inc.
Matt Brown, BSc – Transpharmation Inc.
John Huxter, PhD – Transpharmation Inc.
Lauren Stam, MSc – Transpharmation Inc.
Guy Higgins, PhD – Transpharmation Inc.
Rationale: Corneal kindling in mice models epileptogenesis as well as robust comorbid behavioral phenotypes (hyperactivity, sensorimotor gating deficits, impaired nesting) that serve as analogues of endophenotypes seen in human epileptics. We set out to (1) characterize these emergent behaviors in C57BL/6J mice and (2) determine whether levetiracetam (LEV) not only slows seizure acquisition but also ameliorates associated comorbidities often poorly managed in the clinic.
Methods: Male C57BL/6J mice (8–10 weeks) received twice-daily bilateral corneal stimulations (2 mA, 60 Hz, 3 s) until reaching consecutive stage-4/5 seizures (fully kindled). Mice were pretreated 1 hour before each stimulation with LEV (60 mg/kg, i.p.) or vehicle. After reaching asymptote, animals were evaluated for locomotor activity (distance, rearing), risk-taking in the canopy test, nest-building (5 h score), acoustic startle, and PPI. Spontaneous behavior was also recorded with 3D depth cameras and analyzed using Motion Sequencing (MoSeq), a machine-learning approach that parses behavior into discrete units (“syllables”) for quantitative profiling.
Results:
Seizure progression: LEV significantly delayed onset of fully kindled seizures (mean stimulations: vehicle 8.4 ± 0.6 vs LEV 18 ± 1.6; p < 0.0001).