Study of glial cell function during brain ischemia

脑缺血时胶质细胞功能的研究

• 批准号: 14580792
• 负责人: YAMAMOTO Satoshi
• 金额: $ 2.3万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580792/
• 关键词: Glial cell; Astrocyte; Brain ischemia; Patch-clamp; Membrane current; Glutamate; Glutamate receptors

Purpose : Study of functional changes in electrical membrane properties and chemical receptivity of astrocytes during in vitro ischemia.Method : Using whole-cell patch-clamp techniques, membrane currents were monitored from single cultured astrocyte, and the effects of in vitro ischemia on the electrical membrane properties and receptivity for neurotransmitter, glutamate were examined. Ischemic condition was made by perfusing cells with glucose-free and metabolic inhibitor-containing solution instead of normal artificial cerebrospinal fluid.Results : Ischemic solution caused a transient inward current followed by a slow outward current in the membrane of astrocytes recorded. From the reversal potential, it was suggested that chloride channels and potassium channels might be involved in the generation of the transient inward currents and the slow outward currents, respectively. Glutamate caused inward currents in the astrocyte. The glutamate-induced currents were inhibited by NMDA and non-NMDA glutamate receptor antagonists by about 50%, indicating that astrocytes have not only ionotropic glutamate receptor but also metabotropic glutamate receptors and/or glutamate transporters. The glutamate-induced currents were not modified by ischemic condition in the early time. Due to difficulties of continuous recording, the late effect of ischemia could not be monitored.Conclusion : The astrocyte that has been seemed to be a ischemia-resistant cell, behaves like as the neuron in the electrical membrane properties against ischemia. This suggests that glial cell function can be altered during ischamia, so that maintenance of extracellular concentrations of potassium and neurotransmitters by glial cells might be disturbed.

目的：研究在体外缺血期间，星形胶质细胞的功能变化和化学接受性。方法：使用全细胞贴片钳技术，从单个培养的星形胶质细胞中监测膜电流，以及在体外缺血的影响对电膜的特性和对神经疗法的效果的影响。缺血状态是通过用无葡萄糖和代谢抑制剂溶液而不是正常人造脑脊液的灌注细胞来使缺血状况。溶液：缺血溶液导致瞬时向内电流，然后在记录的星形胶质细胞膜上向外电流缓慢。从逆转电位中，提出氯化物通道和钾通道可能分别参与瞬时向内电流和缓慢的向外电流的产生。谷氨酸在星形胶质细胞中引起向内电流。 NMDA和非NMDA谷氨酸受体拮抗剂抑制了谷氨酸诱导的电流约50％，这表明星形胶质细胞不仅具有离子型谷氨酸受体，还具有分类的谷氨酸受体和/或/或/或谷氨酸转运蛋白。谷氨酸诱导的电流在早期没有通过缺血状态来改变。由于连续记录的困难，无法监测缺血的后期作用。判断：似乎是一种耐缺血的细胞的星形胶质细胞，就像对缺血性缺血性质的电膜特性中的神经元一样。这表明在缺字节期间可以改变神经胶质细胞功能，因此可能会干扰细胞外钾和神经递质的细胞外浓度。

项目成果

Saitoh.M., Yamamoto, S.他: "Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association with intracellular Ca^<2+> rise and mitochondrial damage independently of caspase-3 activation."Brain Research. 991. 187-194 (2003)

Saitoh.M.、Yamamoto, S.等人：“花生四烯酸过氧化物诱导细胞凋亡性Neuro-2A细胞死亡，与细胞内Ca 2+ 升高和线粒体损伤相关，与caspase-3激活无关。”Brain Research 991。 187-194（2003）

Tozaki, H., Yamamoto, S.他: "The inhibitory and facilitatory actions of amyloid-beta peptides on nicotinic ACh receptors and AMPA receptors"Biochem Biophys Res Commun. 294. 42-45 (2002)

Tozaki，H.，Yamamoto，S.等人：“淀粉样蛋白-β肽对烟碱ACh受体和AMPA受体的抑制和促进作用”Biochem Biophys Res Commun.294.42-45(2002)。

Niiyama, S., Yamamoto, S.et al.: "Bupivacaine, but not tetracaine, protects against the in vitro ischemic insult of rat hippocampal CA1 neurons."Neurosci.Res.. 42. 231-241 (2002)

Niiyama, S., Yamamoto, S.et al.：“布比卡因（而非丁卡因）可保护大鼠海马 CA1 神经元免受体外缺血性损伤。”Neurosci.Res.. 42. 231-241 (2002)

Ohta, K., Yamamoto, S.et al.: "Stearic acid facilitates hippocampal neurotransmission by enhancing nicotinic ACh receptor responses via a PKC pathway."Brain Res.Mol.Brain Res.. 119. 83-89 (2003)

Ohta, K., Yamamoto, S.等人：“硬脂酸通过 PKC 途径增强烟碱 ACh 受体反应，从而促进海马神经传递。”Brain Res.Mol.Brain Res.. 119. 83-89 (2003)

Miyamoto, H., Yamamoto, S.et al.: "2-pyrrolidinone induces a long-lasting facilitation of hippocampal synaptic transmission by enhancing alpha? ACh receptor responses via a PKC pathway."Brain Res.Mol.Brain Res.. 117. 91-96 (2003)

Miyamoto, H.、Yamamoto, S.等人：“2-吡咯烷酮通过 PKC 途径增强 α?ACh 受体反应，从而诱导海马突触传递的持久促进。”Brain Res.Mol.Brain Res.. 117