Several models of epilepsy based on chemoconvulsant exposure or electrical stimulation use a lengthy seizure period, which after a variable latent period of 1 to 3weeks, results in spontaneous recurrent seizures. However it is known that the specific duration of the status epilepticus is an important factor, with seizures lasting longer than 40-50min causing discrete differences in pathology and gene expression (1). In this report we implement a short seizure model of rat epilepsy (2) and find spectroscopic changes that predict subsequent histology and metabolism.A short variant of the rat Hellier-Dudek (3) intraperitoneally injected kainate (KA) model of temporal lobe epilepsy was used. After initiation of a stage 3/4/5 seizure, continuing status epilepticus was maintained for 45min after which 20mg/kg diazepam was administered for recovery. Animals were then evaluated twice by MR, 3days and 3weeks after status during the epileptogenesis period. Controls were similarly treated with sterile saline. A Bruker Biospec 7T 40cm horizontal MR system was used with a 72mm volume transmit coil and 2 element receive array. T2 RARE was acquired for positioning of the hippocampus (Fig.1). Over the hippocampal slice, Bolero was used for B0 shimming (3), achieving homogeneity of 5.8±1.0Hz. Single voxel MR spectroscopy was acquired from 8μl 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, accepting Cramer Rao limits of <15%. A subset of animals (n=8) was sacrificed after 3weeks for histological analysis.Fig. 1 shows the positions of the dentate gyrus (DG), CA3 voxels and corresponding DG spectra from a single rat studied at 3days and 3weeks. At 3days, all treated rats (n=21) showed a significant decline in NAA/tCr, increased Ins/tCr, Gln/tCr and Lac/tCr in comparison to control (n=10). Given the possibility that these animals might show substantially variable injury, we evaluated the animals using a histogram analysis with the 3day DG data. As shown in Fig2A (for each animal there is a left and right measurement), a large number of the kainate treated animals exhibited a comparatively normal NAA/tCr, while a minority exhibited low values (<=1.0), this seen in spite of the group increase in Ins/tCr (consistent with occurrence of status). The distribution appears distinct from the control animals (n=10). As the lowest value from the control animals was above 1.0, this was used as the threshold value to segregate the kainate treated animals. To demonstrate this specific behavior from NAA/tCr, Fig2B shows the equivalent histogram for Ins/tCr, which appears to be more consistent with a single group with a large variance. Of the n=21 KA treated rats, a 3day NAA/tCr threshold of 1.0 in the DG separated the animals into n=6 (“KA more injured” KMI with NAA/tCr<1.0) and n=15 (“KA less injured” KLI, NAA/tCr>1.0). This segregation is reflected in the other metabolite changes and the 3week data (Fig. 3). At 3days, the KLI and KMI groups differed significantly from control in Glu/tCr, Ins/tCr, Gln/tCr and Lac/tCr. The majority of these changes are consistent with the KMI group experiencing more intense status and/or slower recovery from the status, with increased inositol, glutamine and lactate. The separation of the KLI and KMI groups persisted into 3weeks. Both groups exhibited some recovery of NAA/tCr, but KLI returned to control values at 1.28±0.12, while the KMI group NAA/tCr value stayed depressed at 1.00±0.12 (control, 1.30±0.15). The 3week KMI group also continued to show a increased Ins/tCr and a decreased Glu/tCr. In contrast, the 3week KLI group had largely normalized all of its metabolic parameters. Histologically, a blinded semi-quantitative Nissl analysis of the dorsal hippocampus was performed in n=8 treated rats, finding that the KLI group (n=4) to be largely intact while the KMI (n=4) group typically showed neuronal loss and gliosis. Overall, the histological data suggest that the 3day segregation by NAA/tCr is predictive towards the 3week histological features of gliosis and Nissl loss.Using a short version Hellier Dudek model, the 3day MR spectroscopic measurement of NAA/tCr can separate the less and more severely injured animals. This is based on the numerous 3day, 3week parameters and histology that are consistent with the KLI or KMI categorization and argues for a key role of neuronal mitochondria and metabolic dysfunction in describing or predicting tissue response in the post-status period. Whether or not NAA/tCr can predict development of epilepsy or cognitive injury after seizures will require additional work.