Response: Development of Temporal Lobe Epilepsy in 21‐day‐old Rats

Abstract

To the Editor: We read with interest the comments sent on our article (1) to the Editor of Epilepsia. When considering all forms of epilepsy, we found indeed a percentage of P21 rats becoming epileptic after lithium-pilocarpine status epilepticus (SE) that was well within the range of that Sankar et al. (2) reported. However, we distinguished subgroups in our P21 epileptic animals. In a previously published article (3,4), only 24% of the P21 rats became spontaneously epileptic, whereas 43% developed seizures when handled or stressed. Our recent data still show these differences, and in our magnetic resonance imaging (MRI) article, within the 83% of P21 rats that became epileptic, a third of them had spontaneous seizures, another third seizures triggered by stress or handling, and another third, both types of seizures (1), which altogether brings the percentage of spontaneously epileptic rats close to that obtained by Priel et al. (5) in the same category of age. Given the heterogeneity in the development of epilepsy in the P21 age group, we focused our research on trying to find a discriminative feature that would occur early enough after SE to predict as early as possible whether P21 rats would become epileptic. For that purpose, we needed a noninvasive technique that would allow keeping the animals alive. With MRI in adult animals subjected to lithium-pilocarpine SE, the only structures that displayed a change in the T2-weighted signal were the basal cortices (entorhinal and piriform), thalamus, amygdale, and hippocampus (6), despite a well-known much larger circuit of the seizures that we had identified previously by using c-Fos immunohistochemistry (7) or quantitative [14C]2-deoxyglucose autoradiography (8). By using MRI in P21 rats, we confirmed the rapid cortical reactivity on the T2-weighted image and were able to correlate this change in signal intensity with the epileptogenic fate of the P21 rat (1). Despite the known involvement of thalamus, amygdale, and substantia nigra in addition to the cortices in the seizure circuit, as shown by Sankar et al. (9), and our own work (7,8), we were unable to detect any signal-intensity change in those structures with the 4.7-T magnet that is at our disposal. Most likely with higher field magnets, the spatial resolution of the images will be improved and allow detection of changes also in other structures critical for the epileptic circuit. The purpose of our MRI article in P21 rats (1) was mainly to develop a reliable noninvasive technique to allow the identification of the epilepsy-sensitive population in P21 rats that we could achieve. We had no intention of delineating a precise seizure circuit because our work with MRI in adult rats, in which the intensity of SE is much stronger and the extent and intensity of damage more pronounced than at P21, did not allow seeing changes in signal intensity throughout the whole epileptic circuit (6). The seizure circuit is more efficiently mapped by other techniques such as c-Fos immunohistochemistry or [14C]2-deoxyglucose autoradiography, which we have applied previously during the acute (7,8), silent (4,10), and chronic phases of the lithium-pilocarpine model of epilepsy in P10, P21, and adult rats (3,4).