| Objective: For providing experimental basis about the study of the rats' brain function and positioning the epileptic lesions, at the same time, helping diagnosis, treatment and prognosis assessment of the human' brain with neuronal migration disorders,we have explored the rats induced by X-ray intrauterine irradiation with neuronal migration disorder about the 2-[18F]-fluoro-2-deoxy-D-glucos micro-PET/CT features in the infancy, adolescence and adulthoods. Methods: In this experiment 17 days-pregnant SD rats were irradiated by X-ray linear accelerator. The dose which were group A?0cGy?, group B?175 cGy?, group C?195cGy? and group D?215 cGy? was different. We randomly selected five rats which were the first offspring?F1? of the pregnant SD rats every group, performed the following contents.?1?We observed the behavior of the selected five rats by video monitoring after the birth of six months, and we selected one day every six days, observing whether there had epileptic seizure.?2?These experimental rats were injected 2-[18F]-fluoro-2-deoxy-D-glucose by the caudal vein after general anesthesia in the infancy?P28?, adolescence?P50? and adulthood?P77?, then we analyzed effects on brain glucose Metabolism and brain volume by micro-PET/CT.?3? These experimental rats were detected the spatial learning and the ability of memory by Morris water maze, including navigation and space search.?4? These experimental rats were detected by intracranial EGG after positioning six parts which were left and right frontal lobe, left and right parietal lobe, left and right hippocampus, testing time was 30 min every part. Then we analyzed the times of seizure every minute?frequency of seizure waves?.?5? In the end we were got the brain of all the experimental rats by craniotomy and Nissl staining. Then we classified these brain according to the classification of FCD. Results:?1? The number of rats about spontaneous seizures were 0, 2, 2, 1in Groups A, B, C, D, respectively in the video recordings selected. The total times of spontaneous seizures were 61 in the model groups, and the incidences of spontaneous seizures were 32.78%, 44.2%, 22.95% in Groups B, C, D,respectively. The total duration of spontaneous seizures of group B, group C, group D were significantly longer compared to the group A?P<0.05?, gradually increasing with the increases in irradiation dose. The difference about the duration of the group D was statistically significant compared to the groups A, B, C, but there was no significantly difference between group B and group C.?2? Micro-positive emission tomography? micro-PET? imaging showed that in the NMD model groups the left and right cerebral hemisphere were smaller and thinner compared to the group A by our visual analysis. Glucose metabolism in the left and right cerebral hemisphere were significantly decreased in the NMD model groups in comparison with the normal control group?P<0.05?, gradually decreasing with the increases in irradiation dose, and glucose metabolism was least in the temporal lobe among all of the rats. In the mature group C and group D were significantly different from group B about the parietal lobe?P<0.05?, and group D were significantly different from group C about the frontal lobe?P<0.05?. At the same time in the mature group D were significantly different from group B about the amygdaloid nucleus?P<0.05?. In the same irradiation dose glucose metabolism were decreased, gradually decreasing with the increasing age. The difference was significant between immature and mature?P<0.05?in the parietal lobe about group D. The other difference was not significant. Glucose metabolism were decreased in the the corpus callosum all the NMD model groups by our visual analysis. Brain volume of all the NMD model groups were significantly reduced compared to the group A?P<0.05?, gradually decreasing with the increases in irradiation dose, but there was not significantly difference among the NMD model groups. All the changes of the left cerebral hemisphere were not significantly difference compared to the right cerebral hemisphere in the same regions. Glucose metabolism were not significantly difference among all the rats in the cerebellum.?3? Place navigation Analysis: the escape latencies of model mature rats were notly longer than that of normal group every day, the differences were statistically significant?P <0.05?, with the increasing times of training, escape latencies gradually shortened, but still longer than normal group. The contemporary model rats' escape latencies put up a positive related to X radiation dose, and the differences were not statistically significant. Space search: the number of platform-crossing frequency of model mature rats were markedly less than that of normal group?P <0.05?, and the percent time traveled in target quadrant were lower than that of normal group?P <0.01?, both the difference were statistically significant. As X-radiation dose increased, the number of platform-crossing were less in model groups,same as the percent time traveled in target quadrant, but the differences were no statistically significant.?4? Every group could been observed epileptiform waves in EEG comparing with normal group, the model groups' median of average number of epileptic seizures per minute was much more?P <0.05?, group A- D were respective 1.25 times /min,8.51 times /min,16.13 times / min, 11.79 times / min, no unilateral advantage was noticed, the difference of the same parts among the model groups were not statistically significant.?5? All the NMD models were proved successful. In the specimen, every model rats could been observed that brain hemisphere had shrunk and was far away from the other, brain tissue volumes were smaller. Callosal agenesis or absence were found. Cortical thinning and bilateral lateral ventricle became larger. Nissl staining displayed all the NMD models had heterotopic gray matter, hippocampal formation of abnormal nodules, the corpus callosum developmental disorders or missing?100%?, cortical layer structural disorder, ectopic neurons, dysmorphic neurons and other abnormalities structure. According to the FCD classification, our models showed that FCD Ia accounted for 33.3%? 5/15?, FCD Ib accounted for 53.3%?8/15?, FCD IIa accounted for 26.7%? 4/15?. As the increasing of X-ray irradiation dose, the difference of pathological features were more obvious. Conclusion : Micro-positive emission tomography?micro-PET? imaging showed that Glucose metabolism in the left and right cerebral hemisphere were significantly decreased and brain volume were significantly reduced in the NMD model groups in comparison with the normal control group, gradually decreasing with the increases in irradiation dose. The corpus callosum were abnormal and deficiency all the NMD model groups by our visual analysis. Glucose metabolism were decreased gradually with age in the same irradiation dose of X-ray. The NMD rats had cognitive dysfunction by Morris water maze experiment,so this model could help further study the pathogenesis of epilepsy associated with cognitive dysfunction. |
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