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

(1)中枢神经系统疾病大鼠模型的制备：采用单侧黑质注射6-OHDA制作偏侧帕金森病大鼠模型。成年大鼠一侧大脑中动脉闭塞，幼年大鼠一侧颈总动脉结扎低氧(8%氧气)造成脑缺血。采用3-硝基丙酸诱导大鼠Huntington病病样症状和纹状体损伤。(2)上述疾病的体外模型：用缺氧缺糖新皮质脑片模拟脑缺血。由于NMDA受体的敏感性，LayrII/III层锥体细胞比其他层的锥体细胞更容易受到钙超载的影响。我们还发现，GABA可能直接和/或通过介导谷氨酸-NMDA兴奋毒性而加重缺血损伤，这是由于缺血时E&lt；el-gt；移动所致。3-硝基丙酸…灌流培养的纹状体和皮质胶质细胞模型大鼠脑片移植神经元生理学实验：建立受者帕金森病模型和脑缺血模型大鼠脑片活体细胞的标记和鉴定方法。从标记鉴定的移植细胞中成功地记录到电压依赖性的Na~+和K~+电流以及谷氨酸引起的细胞内Ca~(2+)和Gt；升高。3-硝基丙酸诱导的亨廷顿病样纹状体损伤模型大鼠诱导型一氧化氮合酶基因表达的检测：免疫组织化学染色显示，在3-硝基丙酸诱导的亨廷顿病样纹状体损伤中，诱导型一氧化氮合酶的表达增加。较少

(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