| objective: For laying the foundation for further study of the pathogenesis of tuberous sclerosis and epileptogenic mechanism, we have investigated the main pathological features of brain, heart, kidney, skin, eyes, lung and teeth of the tuberous sclerosis rat models induced by X-ray intrauterine irradiation. methods:(1) Eight 17 days-pregnant SD rat was randomly divided into four groups: normal control group(2 rats), 175 c Gy X-ray irradiated group(175c Gy group, 2 rats), 195 c Gy group(2 rats) and 215 c Gy group(2 rats). The first offspring(F1) of the pregnant SD rats were applied for our experiments.(2) F1-rats were applied for 24 hours behavior dynamic observation for 30 consecutive days when they are two months old. We observed the activities, feeding, drinking, circadian rhythm to understand whether the spontaneous seizures occured.(3) The ability of spatial learning and memory was determined by Morris water maze through positioning navigation, space exploration and visualization platform experiments.(4) And intracranial EGG was detected by locating electrode needles in the bilateral frontal, parietal cortex, hippocampus.(5) All rats were sacrificed by cardiac perfusion fixation for photographing the abnormal specimens and the multi-organ pathological examination including measurement of the brain volume and weight, HE staining and Nissl staining. results:(1) There were no spontaneous seizures taking place in normal control group. Night activities such as wash-face movement, itchiness and chasing were more frequently observed of the rats in X-ray irradiated groups than those in normal control group. Furthermore, we found above third grade spontaneous seizures classified by Racine classification occurred on three rats in X-ray irradiated groups and the incidence is 16.7%.(2) In Morris water maze test, the incubation period of the rats in X-ray irradiated groups was significant longer than that of the rats in normal control group(P<0.05). The percentage of the time stayed in the target quadrant and the number of crossing the platform were markedly increased(P<0.05). And there is no significance between X-ray irradiated groups.(3) EGG showed that frequent epilepsy waves were found in the cortex of frontal and parietal lobe and hippocampus on the rats in X-ray irradiated groups. Little epilepsy waves were observed on the rats in normal control group. The median incidence of epilepsy waves per minutes was 0.9, 8.3, 15.5, 12.1 of normal control group, 175 c Gy group, 195 c Gy group and 215 c Gy group respectively(P<0.01). The maximum amplitude of epilepsy wave was located in hippocampus and the minimum was located in cortex of frontal.(4) There is no hamartomas observing in all of the rats whose skin and peri-nail were normal. The volume and weight of brain were smaller of the rats in X-ray irradiated groups than that of the rats in normal control group. And exposed quadrigeminal body, incomplete corpus callosum and expanded ventricular system were observed in the rats in X-ray irradiated groups. Moreover, the heterotopic nodules located in cortex and subcortex were detected by Nissl staining. The abnormal structure of hippocampus was manifested by dispersive arrangement of neurons in CA1, CA2, CA3 regions and heterotopic nodules in CA1 region. In addition,one rats with a larger kidney, which were nephroblastoma verified by immunohistochemistry were observed in 215 c Gy group. conclusion:(1) Tuberous sclerosis characterized by abnormal cortex, subependymal nodules, epilepsy and disturbance of intelligence was well established in the F1 rats by X-ray irradiating 17 days-pregnant SD rats. But we did not find the damages in organs despite brain.(2) As the irradiation dose increased, the extent of the damage of the brain tissue and disturbance of intelligence gradually increased. But there is no changes in the brain epileptic discharge.(3) This model is easy to achieve, the operation is simple, the death rate is low. Such advantages provide the reliable bases to study the pathogenesis and pathogeny of tuberous sclerosis. |
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