Abstracts

LITHIUM PILOCARPINE-INDUCED STATUS EPILEPTICUS IN THE IMMATURE RAT RESULTS IN AGE-SPECIFIC NEURODEGENERATION: A COMPARISON OF THREE AGES USING FLUORO-JADE B AND A NOVEL MINIATURE VIDEO-EEG TELEMETRY SYSTEM

Abstract number : 3.287
Submission category : 13. Neuropathology of Epilepsy
Year : 2013
Submission ID : 1751380
Source : www.aesnet.org
Presentation date : 12/7/2013 12:00:00 AM
Published date : Dec 5, 2013, 06:00 AM

Authors :
E. Scholl, M. Lehmkuhle, F. Dudek, J. Ekstrand

Rationale: Many animal models of acquired epilepsy have demonstrated that the immature brain is more prone to seizures but also more resistant to seizure-induced neuronal injury than the adult brain. However, because of technical difficulties obtaining EEG recordings in pre-weaned animals, our knowledge of electrographic activity during status epilepticus in pups younger than postnatal day 12 (P12) is limited. A novel miniature wireless telemetry system for immature animals has facilitated a more detailed comparison of age-dependent EEG activity at P7-P21 during status epilepticus to the resultant acute neuronal damage observed 24 h after seizure induction. Methods: Sprague Dawley rat pups were implanted with a miniature wireless telemetry device, and status epilepticus was induced at 7, 13, or 20 days of age with intraperitoneal injection of pilocarpine (50 mg/kg). Animals were pretreated 14-16 h before pilocarpine treatment with LiCl (127 mg/kg). Status epilepticus was monitored for at least 4 h with continuous video-EEG recordings to observe both behavioral and electrographic seizure activity. After 24 h, brain tissue was examined with Flouro-jade B, a marker for degenerating neurons. Results: Lithium pilocarpine provoked prolonged status epilepticus that could be observed by both electrographic EEG recording and clinical behavior. P7 animals displayed low-amplitude, discontinuous, rhythmic polyspike and sharp wave activity. Behavioral correlates included myoclonic jerks, tonic stiffening, single limb clonus, and behavioral arrest. P13 and P20 rats more consistently displayed prolonged higher amplitude spike and wave activity similar to activity observed in adult animals. Behavioral correlates in these older animals consisted of robust tonic-clonic seizure activity with rearing and loss of posture (Racine scale 4-5). Examination with Fluoro-jade B showed minimal damage in P7 rats, with neurodegeneration primarily localized to the anterodorsal thalamus. P13 rats showed increased, but variable, degeneration primarily in midline thalamic nuclei, amygdala, hippocampus, parasubiculum, dorsal endopiriform nuclei, and para limbic corticies (perirhinal, entorhinal, and piriform). P20 rats showed the greatest neurodegeneration that, while still variable, was more consistently present in these areas.Conclusions: EEG seizure activity can be recorded after treatment with lithium pilocarpine in immature animals as young as P7. The electrographic pattern of status epilepticus was qualitatively different in P7 animals compared to older ages. The pattern of acute neurodegeneration from lithium pilocarpine status epilepticus is age specific and increases in extent and severity as a function of age. Status epilepticus in P7 animals appears less severe than in older juvenile animals, which may explain in part the relative lack of neuronal damage in this age group.
Neuropathology of Epilepsy