Abstracts

Rationale: Several groups have reported on the metabolic injury seen during the epileptogenesis period in chemoconvulsant models of epilepsy (1, 2). These changes have been characterized as neuronal and glial in nature, with declines in N-acetyl aspartate (NAA), increases in myo-inositol (Ins) and glutamine. With the non-invasive nature of MR imaging, it has been suggested that MR spectroscopy and imaging may be evaluated for development of a biomarker for epileptogenesis. In this report, we describe the development of a variant of the Hellier-Dudek model studied with MR spectroscopy to identify potential such biomarkers.Methods: A short variant of the Hellier-Dudek (3) low dose kainate (KA) model of temporal lobe epilepsy was used. 180-200g male rats (Charles River) were injected i.p with 5 mg/kg KA (n=17) until a stage 3/4/5 seizure (modified Racine scale) was elicited. Status epilepticus (SE) was defined as the time from first motor seizure started until 45min later when 20 mg/kg diazepam was administered. Lactated Ringer’s was given s.c to facilitate recovery. Controls (n=7) were similarly treated with sterile saline. Rats were evaluated twice by MR, in the post SE state (3days, 3d) and during the latent period (3weeks post SE, 3w). Rats were video monitored 24-7 for the duration of the study. MRI: A Bruker Biospec 7T 40cm horizontal MR system was used throughout with a 72mm volume transmit coil and 2 element receive array. Rapid T2 weighted acquisitions were acquired for positioning of the hippocampus (Fig.1). Single voxel MR spectroscopy was acquired from 8 µl voxels with TR/TE 1.7s/10ms (17min per acquisition) from the left, right dentate gyrus (DG) and CA3 regions. LCM analysis was performed for determination of the metabolite profiles and taken as a ratio to total creatine (tCr), accepting Cramer Rao bounds of <12%.Results: Of the n=17 KA treated rats, a NAA/tCr threshold of 1.0 in the DG acquired at 3d separated the animals into 5 (“KA more injured”, KMI, NAA/tCr<1.0) and 12 (“KA less injured” KLI, NAA/tCr>