Pathology Of Animal Models Of Disorders Of Cortical Development And The Expressions Of Main Neurotransmitter Associated With Epilepsy In Cortex

OBJECTIVE: To study the pathology of animal models of disorders of cortical development and the expressions of main neurotransmitter associated with epilepsy in cortex by the method of histiocyte and molecular pathology. METHODS: Animal models of DCDs were made in two ways.(1)The first was that we used a 1-mm-diameter copper cylinder cooled with liquid nitrogen that temperature below –1960C to injure the cortical plate of neonatal rats (postnatal the day, P0,<24 h).(2)The other way was that pregnant Wistar rats were exposed to γ-ray using a single dose of 1.8 Gy on embryonic day 17(E17) for 191～206 seconds.The brain of their offsprings might receive lesions through this method.The experimental rats were divided into normal control groups,irradiated adult rats and model groups. We observed the following aspects to confirm the success ratio, the credibility, histiocyte and immunohistochemical studies in the animal models of DCDs: ①Postnatal 16～18 and 12～16 weeks,the liquid nitrogen lesion rats and the offsprings of irrated pregnant rats were killed to be used to histomorphology and histopathologic studies.②The expressions of Glu,GABA,NMDAR1,GluR2,GABAAα1 in cortex were observed by immunohisochemistry. RESULTS: (1) An animal models of FCD was made successfully that used liquid nitrogen. All of the neonatal little rats received liquid nitrogen lesions had cortical malformation mimics human microgyria. We can succeed in developing the animal models of DCDs, the method was that pregnant rats were exposed to γ–ray on embryonic day 17. All of the irrated pregnant rats' offsprings were caused brain lesions resuiling in neuronal migration disorders. In the control rat cortex and irradiated adult rat cortex, the typical six-layered lamination is apparent, whereas the model rat cortex shows laminar disorganization and thinning. (2)In addition, there are clusters of large neurons in both superficial and deep layers in the model rat cortex.HE stains and Nissl stains showed the presence of multiple cortical areas of neuronal clustering and a focal three or four layered cortex,more over pyramidal cell dispersion was seen in the hippocampal formations. The morphological alterations with a three- to four- layered microgyrus with neuronal cells loss and disorganization of cells at the bottom of the microsulcus and an inflection of apical dendrites toward the microsulcus.The neuronal staining pattern of large pyramidal cells in the neighborhood of the dysplasia did not differ for any others investigated. A modest enhancement of excitability may occur in CA1 pyramidal neurons of irradiated rats due to diminished network inhibition and possibly aslo to increased synaptic excitability in the region. DCDs could result in mossy fibers sprouting in hippocampi CA3 area. (3)FCD were removed surgically and studied under transmission electron microscope.We found several morphological changes in these specimens: ①Swelling and expanding of interior membrane system. ②Dissociation of plasma membrane and myelinolysis.These might resulting in an increased susceptibility to seizures,leading to further seizures. (4)Animal model groups have less activities than the normal control groups.We observed a few spontaneous seizures. (5) The expressions of Glu,GABA,NMDAR1,GluR2,GABAAα1in cortex were observed by immunohisochemistry. The decreased expression of GABA and GABAAα1 and the increased expression of Glu ,NMDAR1,GluR2 around microgyria in the rats' cortex of FCD may have relationship with the mechanisms of the intractable epilepsy(P<0.05).The expressions of Glu,GABA,NMDAR1,GluR2,GABAAα1 in cortex were observed by immunohisochemistry in the rats' cortex of DCDs.The decreasing expression of GABA and GABAAα1 and The increasing expression of Glu ,NMDAR1,GluR2 around microgyria in the rats' cortex and hippocampi CA1,CA2,CA3 area of DCDs may have relationship with the mechanisms of the intractable epilepsy(P<0.05). CONCLUSIONS: 1. Liguid nitrogen lesion on neonatal rats could result in microgyrus and mossy f...