Membrane Properties, Sunaptic Currents, and Intracellular Ca Transients in Transplanted Neurons in the Model Rats of Diseases of the Central Nervous System

点击翻译按钮获取中文摘要

(1) Preparing Model Rats of Diseases of the Central Nervous System : Hemiparkinsonian disease model rats were made with unilateral injection of 6-OHDA to substantia nigra. Cerebral ischemia was performed by unilateral mid cerebral artery occlusion in adult rats and by unilateral common carotid artery ligation with hypoxia (8% oxygen) in immature rats. 3-Nitropropionic acid was administered intraperitoneously to induce Huntington diesease-like symptoms and striatal lesions in rats.(2) In Vitro Model of the Diseases Described Above : Cerebralischemia was simulated by oxygen-glucose deprivation of neocortical slices. LayrII/III pyramidal cells were more vulnerable to Ca^<2+>-overload than those in the other layrs due to NMDA receptor susceptibility. We also found that GABA may aggravate ischemic damage directly and/or via mediation of glutamate-NMDA excitotoxicity as a result of E_<el> shift during ischemia. Perfusion of cultured striatal and cortical glial cells with 3-nitropropionic aci … More d caused cellular Ca^<2+>-overload leading to necrotic deathby reverse operation of Na^+-Ca^<2+> exchanger.Physiological Experiments on Transplanted Neurons in Brain Slices from the Model Rats : We established methods for labeling and identification of living donor cells in brains slices of recipient himiparkinsonian and cerebral ischemia model rats. Voltage dependent Na^+ and K^+ currents as well as glutamate-induced intracellular Ca^<2+> increase were successfully recorded from the grafted cells identified by the labeling. Interconnection between the host and grafted cells was functionally proved in brain slices as intracellular Ca^<2+> transients in response to the electrical stimulation of neighboring host tissue.Detection of Gene Expression Induced in the Model Rats : In the 3-nitropropionic acid-induced Huntington disease-like striatal lesion, expression of iNOS mRNA increased as revealed by RT-PCR method Immunohistochemical staining also showed an increased level of iNOS in parallel with mRNA. Less