The Temporospatial Distribution of Glutamate Receptors and the Effect of MK-801 on Glutamate Receptors Activation in Kainate-induced Seizure Model: Quantitative Receptor Autoradiography of Ionotropic Glutamate Receptors

BACKGROUND: Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Some evidence indicates that selective down regulation of AMPA receptor may be the mechanism of delayed neuronal cell death in the hippocampus. METHODS: We used in situ hybridization to examine the hybridization density (HD) of NMDA and AMPA receptors on excitotoxicity and epileptogenesis in the hippocampus of the kainic acid (KA)-induced rat seizure model. Some Sprague-Dawley rats were injected with KA, and others with MK-801 prior to KA injection. The rats were killed at 8 hours or 4 weeks after KA or MK-801/KA injection. HD of [3H]MK-801 and [3H]AMPA bind-ing in subfields of the hippocampus was measured by an image analyzer. RESULTS: After 8 hours of KA injection, [3H]MK-801 binding was increased in CA1 and CA3, and decreased in dentate gyrus, and [3H]AMPA binding was decreased in all of CA1, CA3 and fascia dentata, and pretreatment of MK-801 did not affect [3H]AMPA binding in all of CA1, CA3 and dentate gyrus. After 4 weeks, both [3H]MK-801 and [3H]AMPA binding were prominently increased in inner molecular layer of dentate gyrus. CONCLUSIONS: Glutamate receptors, especially NMDA receptor, were associ-ated with excitotoxicity in the hippocampus but the selective down regulation of GluR2 subunit of AMPA receptor without NMDA receptor activation may not be sufficient to cause excitotoxic neuronal cell death in CA1 and CA3. In addition, the synaptic reorganization in inner molecular layer of dentate gyrus was proved to be chronically hyperex-citable in function and may contribute epileptogenesis.

Neuropathologic studies of cerebral cortical dysplasia

Cortical dysplasia(CD) represents a spectrum of neuropathologic changes reflecting a derangement of the normal process of neocortical development. We have presented 32 patients who underwent cortical recectiom for intractable seizures and demonstrated the neuropathologic features, which could be explained by a disturbance in the process of neural development in the farm. It could be characterized by light microscopic features: cortical laminar disorganization, neurons in the molecular layer, subpial re=ants of granule calls, remnants of marginal glioneuronal heterotopia, neuronal heterotopia in the white matter, polymicrogyria, neuronal cytomegaly and balloon cell change. Even though cortical dyslamimtion was the consistent finding of all the cases, the neuronal cytomegaly and balloon cell change were diagnostic hallmarks in the study. The cytomegatic neurons were strongly reactive to silver impregration and to immunohistochemical marrkers of neurons, such as neurofilament protein (NF, 68 and 200 kDa) and neuron-specific enolase(NSE). They showed hypertrophic endoplmmic reticul= and increased number of mitochondria in their cytoplasm and incomplete synapses in electron microscopic study. The balloon cells were positively stained by glial fibrillary acidic protein, NSE and vimentin and were filled with intermediate filaments in their cytoplasm. These results indicated that both cytomegalic neurons and balloon cells are produced by faulty cell differentiation involving neuroblast in the former, and both neuronal and glial stem cell lines in the latter.