Neuroprotection of postischemic hypothermia in combination with neuroprotective agents against ischemic neuronal damage

缺血后低温联合神经保护剂对缺血性神经元损伤的神经保护作用

• 批准号: 11671504
• 负责人: YASUGI Takumi
• 金额: $ 0.96万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671504/
• 关键词: hypothermia; cerebral ischemia; microglia; propentofylline; theanine; 血液脳関門; 低体温; 局所脳虚血

Many animal experiments have indicated that postischemic hypothermia rescues neurons from transient ischemic damage. The neuroprotection of postischemic hypothermia depends on initiation time, duration, temperature, as well as the degree of ischemic damage. However, when the duration of hypothermia was only several hours and temperature was lowered only a few degrees, the neuroprotective effect of hypothermia was reduced in longer periods of survival. We examined whether short-duration or mild postischemic hypothermia in combination with neuroprotective agents treatment would consistently protect ischemic neuronal damage.Propentofylline (PPF) is known to have an inhibitory effect of microglial proliferation. Short-duration postischemic hypothermia combined with daily PPF (10 mg/kg, ip, for 2 weeks) treatment led to a significant increase in the number of normal CA1 neurons (60%) compared with the non-treated group (6%).γ-Glutamylethylamide (theanine) is contained in high-grade Japanese … More green tea as a natural glutamate analog. We examined the protective effect of theanine on ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One μl of theanine from each three concentrations (50 μM, 125 μM and 500 μM) was administered through the lateral ventricle 30 min before ischemia. Seven days after ischemia, the number of intact CA1 neurons in the hippocampus was assessed. Ischemic neuronal death in field CA1 of the hippocampus was significantly prevented in the theanine-pretreated groups in a dose-dependent manner, with approximately 60% and 90% survival with 125 μM and 500 μM of theanine, respectively. Moreover, we tested a protective effect of short-duration and mild hypothermia in combination with daily theanine treatment on delayed neuronal death in transient forebrain ischemia of gerbils. Theanine was administered daily 5 mg/kg after ischemia for 30 days. After survival of 30 days, the extent of CA1 neuronal damage in the hippocampus was assessed histologically. Short-duration and mild postischemic hypothermia combined with theanine treatment led to significant increase (67% and 72%, respectively) in viable CA1 neurons, compared to the control group (8% survival).These findings indicate that short-duration and mild hypothermia in combination with PPF or theanine has a beneficial effect on ischemic neuronal damage consistently. Less

许多动物实验表明，缺血后低温可以挽救神经元免受短暂性缺血损伤。缺血后低温的神经保护取决于起始时间、持续时间、温度以及缺血损伤的程度。然而，当低温持续时间仅为几个小时且温度仅降低几度时，低温的神经保护作用在较长的生存期内就会减弱。我们研究了短期或轻度缺血后低温与神经保护剂治疗相结合是否能够持续保护缺血性神经元损伤。已知普鲁托茶碱 (PPF) 具有抑制小胶质细胞增殖的作用。短期缺血后低温联合每日 PPF（10 mg/kg，腹腔注射，持续 2 周）治疗导致正常 CA1 神经元数量 (60%) 与未治疗组 (6%) 相比显着增加。γ-谷氨酰乙基酰胺（茶氨酸）作为天然谷氨酸类似物存在于高级日本绿茶中。我们检测了茶氨酸对沙鼠海马 CA1 区缺血性迟发性神经元死亡的保护作用。缺血前 30 分钟，通过侧脑室给予每三个浓度（50 μM、125 μM 和 500 μM）1 μl 茶氨酸。缺血 7 天后，评估海马中完整 CA1 神经元的数量。茶氨酸预处理组以剂量依赖性方式显着预防了海马 CA1 区的缺血性神经元死亡，125 μM 和 500 μM 茶氨酸的存活率分别约为 60% 和 90%。此外，我们还测试了短期轻度低温结合每日茶氨酸治疗对沙鼠短暂前脑缺血延迟性神经元死亡的保护作用。缺血后 30 天，每天给予茶氨酸 5 mg/kg。存活 30 天后，通过组织学评估海马 CA1 神经元损伤的程度。与对照组（8% 存活率）相比，短期轻度缺血后低温联合茶氨酸治疗可显着增加存活的 CA1 神经元（分别为 67% 和 72%）。这些研究结果表明，短期轻度低温联合 PPF 或茶氨酸对缺血性神经元损伤始终具有有益作用。较少的

项目成果

柳瀬尚人: "グルタミン酸毒性と虚血神経細胞死"Brain Medical. 12. 176-180 (2000)

Naoto Yanase：“谷氨酸毒性和缺血性神经元死亡”《Brain Medical》12. 176-180 (2000)。

Yanase H, Kataoka K: "Mechanism of neuronal protection by hypothermia."J Clin Exp Med. 188. 745-749 (1999)

Yanase H、Kataoka K：“低温保护神经元的机制。”J Clin Exp Med。

Cui Y: "Ischemia-induced glutamate release in the dentate gyrus : a microdialysis study in the gerbil"Neurosci Lett. 271. 191-194 (1999)

崔Y：“齿状回缺血诱导的谷氨酸释放：沙鼠的微透析研究”Neurosci Lett。

柳瀬尚人: "脳と神経-分子神経生物科学入門"共立出版. 9 (1999)

Naoto Yanase：“大脑和神经 - 分子神经生物学简介”Kyoritsu Shuppan 9 (1999)。

Yanase H, Kataoka K: "Neuroprotective effect of mild hypothermia in experimental brain ischemia. Brain Hypothermia, Hayashi N (Ed)"Tokyo, Springer-Verlag. 69-82 (2000)

Yanase H、Kataoka K：“轻度低温对实验性脑缺血的神经保护作用。脑低温，Hayashi N（编辑）”东京，Springer-Verlag。