Abstracts

The lithium-pilocarpine model in the rat is a model of temporal lobe epilepsy with the same temporal evolution as in patients. After pilocarpine injection, the animals develop a severe status epilepticus (SE) and, after a mean latency of 14 days, they exhibit spontaneous recurrent seizures. We studied the evolution of the lesions with magnetic resonance imaging (MRI) and the evolution of metabolism with 2DG autoradiography. We used a robust, fully-automated algorithm that has been developed for a tri-dimensional reconstruction of autoradiographic images. We superimposed the anatomical information (MRI) with metabolic data from the same animal to determine the neuronal circuit involved in each phase of the pathology.
SE was induced by lithium chloride (3 meq/kg) 18 h before pilocarpine was injected (25 mg/kg). MRI was performed on a MR scanner operating at 4.7 T. We followed the evolution of lesions, using a T2-weighted sequence. Local cerebral metabolic rates for glucose (LCMRglcs) were measured by the 2DG method at the following times: 2 h, 6 h, 24 h, 1, 3 and 9 weeks after SE.
The most significant changes in metabolism occurred in the first 24 h following SE. Two hours after SE, LCMRglcs dramatically increased in all structures. Six hours after SE, the LCMRglcs were still increased in the hippocampus of all animals. In the piriform and entorhinal cortices and in the thalamus, LCMRglcs was increased or normal according to the rat. Consequently, at this time, 3D autoradiography showed a hypermetobolic circuit either restricted to the hippocampus or including the hippocampus, piriform and entorhinal cortices and the thalamus. No particular neuronal circuit could be outlined by 3D autoradiography 24 h after SE. LCMRglcs returned to control values more rapidly in cortices and thalamus than in the hippocampus which is in accordance with MRI data where edema appeared in the piriform and entorhinal cortices, and the thalamus (24 h after the SE) and only later in the hippocampus (48 h after SE). At 1, 3 and 9 weeks, the coupling of the anatomical and metabolical information showed that the hippocampus is hypermetabolic during the chronic phase of the pathology. MRI images showed also that hippocampal sclerosis worsened over time while LCMRglcs of this structure varied only slightly.
The present data show that 3D autoradiography allows to map the neuronal circuit at various phases of the pathology. The piriform and entorhinal cortex and the thalamus return to control levels of LCMRglcs more rapidly than the hippocampus and are also edematous before the hippocampus. The cortices and the thalamus appear to play a transient key role at the very early phases of epileptogenesis while the hippocampus seems to have a major function for spontaneous seizures during the chronic phase.