Abstracts

Rationale: The hippocampus is organized into a sausage-like structure of several thin transverse slices containing tri-synaptic circuitry, also known as the lamellar organization. Our lab has been interested in the functional rearrangement of epileptic hippocampal circuitry in models and humans with intractable temporal lobe epilepsy. Using anatomical techniques, we demonstrated seizure-induced sprouting interconnecting adjacent hippocampal lamellas in several epileptic models (Cavazos et al, 2004, 2006). More recently, using physiological techniques, we showed translamellar hippocampal hyperexcitability in the Kainic Acid-Status Epilepticus (KA-SE) model. Our studies have shown that seizure-induced sprouting has a latent period followed by progressive and permanent aberrant interconnectivity between hippocampal lamellas, which precedes occurrence of spontaneous seizures of increasing frequency. We extend these observations using functional MRI (fMRI)-BOLD analysis from perforant path (PP) stimulation examining translamellar hyperexcitability in repeated observations in the same KA-SE animal. Methods: Sprague Dawley male rats (200g) were anesthetized (1.5% Isoflurane) and prepared for electrode implantation with a MRI compatible bipolar electrode lowered into PP (-8.0mm,4.2 mm,3.5 mm). Electrodes were anchored with 4 nylon screws and dental cement. Rats had 7 day postsurgical recovery and given analgesics and topical antibiotics. fMRI experiments were performed on a Bruker Biospec 11.7T scanner with surface coil. T2 weighted spin echo images were obtained using rapid acquisition relaxation enhanced (RARE) and echo planar imaging (EPI) sequences. Baseline fMRI scan was triggered by hippocampal stimulation with a stimulation block of 7 trains with 10 sec stimulation and 50 sec rest per train. The block was repeated at 2.5, 5, 10, and 20 Hz with 1.0mA current. Images were saved and analyzed with Stimulate software. Kainic Acid (KA), 5mg/kg i.p. every 1 hr (x3) was injected into rats. They were observed for 5 hrs post-KA to verify status epilepticus (SE). Only rats with SE for 30+ min were used in study. Rats were re-scanned at 7, 21, 60, and 90 days after KA-SE. Results: Ten rats were implanted and are undergoing experimentation. At baseline scans, PP stimulation induced BOLD response signal was observed at 5, 10 and 20 Hz in a 2-4 mm region of the dorsal hippocampus. At 7 days after KA-SE, during the latency period, there was no additional BOLD response recruitment in hippocampal lamellas above or below the initial activation observed in the baseline fMRI scans. Conclusions: PP stimulation is able to trigger a pattern of hippocampal lamellar fMRI activation. At 7 days after KA-SE, no translamellar hyperexcitability was observed in agreement with previously described anatomical and physiological observations of a latency period. Patterns of fMRI hippocampal activation might be useful neuroimaging surrogate markers that might help define phenomenon of translamellar sprouting, a potential mechanism for epileptogenesis.