| The lithium-pilocarpine rat model of epilepsy reproduces most of the features of human temporal lobe epilepsy, and becomes a popular topic in the epilepsy research after 2000. This model of epilepsy in rats has three distinct periods: (1)an acute period, the first 24h after that built up progressively into status epilepticus (SE) by Li-Pilocarpine injection; (2)a silent period, the rat with a progressive normalization of EEG and behaviour which about 15 days after acute period; (3)a chronic period with spontaneous recurrent seizures (SRS). It recurs several times per week and the main features of the SRS observed during the long-term period resemble those of human complex partial seizures. And there isn't any report about the 'H-MRS changes of this lithium-pilocarpine model till now.This study investigates the progressive changes in the brain especially in the hippocampus of the rats before appearing chronic period onset of spontaneous recurrent seizures (SRS) in the epilepsy model and search for basic mechanisms of epileptogenesis.Status epilepticus was induced in adult rats by repeated injection of low doses of pilocarpine(10~15mg/kg) after 24h of lithium administration. After onset of Status epilepticus for 1 hour, the animals were treated with diazepam. The rats established spontaneous recurrent seizures after some days with normal behaviors.All of the rat models of epilepsy were divided into 7 groups randomly, the examinations were taken on those groups at different time points: 3 hours, 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks after pilocarpine-induced status epilepticus (SE), and compared with a normal control group. MRI and pathological examination were used to detect the morphological changes. T1, T2weight sequence and volumetry of the hippocampus were preformed on a 1.5 MRI system. The hippocampus extract was measured using 'H-MRS on 9.4T condition to define the changes of NAA, Cho, Cr, GAB A and glutamate in it. The GABAA and glutamate (NMDA) receptors changes in the hippocampus also were examined at each time point by western blot. All the statistics was preformed on SPSS 10.0 software package by One-way ANOV (Analysis of Variance) to compare the mean between 8 groups and Dunnett t test to compare each epilepsy group with the normal control group.The results display multiple abnormal metabolic and morphological changes on the Li-pilocarpine rat model before the onset of spontaneous recurrent seizures in chronic peroid:1. At acute period, there was a highly elevation of Glu/Cr level in the hippocampus on 'H-MRS at 3 hours after status epilepticus (F=2.465, P=0.047), and hyper signals appeared in the amygdala, the piriform and entorhinal cortex on MRI T2WI. And hyper signals can also be found in the sensor-motor cortex area, but it disappeared 24 hours after SE. But edema can be found in the amygdala, the piriform and entorhinal cortex, the hippocampus and the thalamus at this time. Also the NAA/Cr level in the hippocampus on 'H-MRS began to decrease from 24 hours after SE (F=5.813, P=0.001).2. At silent period, the expression of glutamate NMDA receptor in the hippocampus was elevated from 3-7 days after SE (F=4.566, P=0.006). 3 days after SE, the NAA/Cr level in the hippocampus decreased from normal 0.6272 + 0.0335 to 0.4466 + 0.0578, obviously edema can be found on MRI in the hippocampus, but the edema of thalamus was remitted; 7 days after SE, the NAA/Cr level in the hippocampus continually decreased to 0.4352+0.0486, the edema of amygdala was remitted, but the high signal on MRI T2WI in the hippocampus still exist. 14 days after SE, the NAA/Cr level in the hippocampus decreased to 0.4038 + 0.0376. The volumetry showed bilateral atrophy of the hippocampus (F=20.131, P<0.001). And enlarged cerebral ventricular also can be found on MRI at this time. 'H-MRS showed the GABA/Cr level in the hippocampus decreased from this time (F=11.518, PO.001). The expression of itsreceptor, GABAA receptor al subunit in the hippocampus also decreased (F=8.493, P<0.001).
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