Abstracts

The aim of this study was to test weather or not unilateral excitotoxic hippocampal lesion in immature rats could induce epileptogenesis. Experiments were performed in 12-day-old Wistar rats (P12; n=49). NMDA in doses of 50, 75 and/or 90 nmol (pH 7.4) was injected in a volume of 0.5 [mu]l into the dorsal hippocampus under halothane anesthesia. Controls received the same volume of solvent. Pattern and duration of NMDA-induced convulsions was registered. Registration electrodes were implanted into the dorsal hippocampus and the sensorimotor cortex four months after NMDA application. Animals were video/EEG monitored for one week to detect seizures, then they were given an overdose of urethane and the brains were prepared for histology. Severity and extension of damage was evaluated from Nissl-stained sections. Timm staining was used to evaluate mossy fiber sprouting and the density of sprouting was scored from 0 (no sprouting) to 5 (confluent dense band of sprouting covering the entire inner molecular layer). All three doses of NMDA immediately induced motor status epilepticus lasting approximately 4 h. No dose-related differences were found in intensity or pattern of convulsions. There was also no difference in mortality between controls and experimental groups ([lt] 10% rats died in every group). Four months after SE, EEG analysis demonstrated presence of epileptiform graphoelements consisting of spikes or sharp waves in all animals receiving NMDA. Nonconvulsive seizures were formed by series of spikes in both hippocampi with a moderate spread to the neocortex. They were accompanied by behavioral arrest or automatisms were also recorded. Percentage of animals exhibiting seizures increased from 43% to 75% in a dose-dependent manner. Morphological evaluation revealed extensive unilateral lesions and gliosis on the site of injection. In addition to the hippocampus the thalamus was also involved. Extension of lesion was clearly related to the dose of NMDA. Mossy fiber sprouting was present in all experimental animals and it was significantly more intense on the side of injection (1.8+0.2, 2.6+0.3 and 3.0+0.1, respectively, for the three doses of NMDA) than contralaterally (1.0+0.1, 1.1+0.2 and 1.2+0.1, respectively). There was no significant difference among these individual doses in intensity of sprouting. Intrahippocampal injection of solvent never resulted in an increase of sprouting density (0.6+0.1 and 0.7+0.1 for the side of injection and contralateral hippocampus, respectively). Excitotoxic damage combined with status epilepticus early in development resulted in morphological damage, mossy fiber sprouting and development of epilepsy later in the development. (Supported by a Center for Neuropsychiatric Studies, project No.LN00B122)