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

许多动物实验表明，缺血后低温可挽救短暂性缺血损伤的神经元。缺血后低温的神经保护作用与低温的起始时间、持续时间、温度以及缺血损伤的程度有关。然而，当低温持续时间仅为几个小时，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会降低。我们研究了短期或轻度缺血后低温联合神经保护剂治疗是否能持续保护缺血性神经元损伤。丙戊茶碱（PPF）已知具有抑制小胶质细胞增殖的作用。短时间缺血后低温联合每日PPF（10 mg/kg，ip，持续2周）治疗导致正常CA 1神经元数量（60%）比未治疗组（6%）显著增加。 ...更多信息 作为天然谷氨酸盐类似物的绿色茶。我们研究了茶氨酸对沙土鼠海马CA1区缺血性迟发性神经元死亡的保护作用。在缺血前30 min经侧脑室注射50 μ M、125 μ M和500 μ M茶氨酸各1 μ l。缺血7天后，评估海马中完整的CA1神经元的数量。在茶氨酸预处理组中，海马CA1区的缺血性神经元死亡以剂量依赖性方式显著预防，125 μ M和500 μ M茶氨酸分别约有60%和90%的存活率。此外，我们测试了短期和轻度低温结合每日茶氨酸治疗对沙土鼠短暂性前脑缺血迟发性神经元死亡的保护作用。缺血后每日给予茶氨酸5mg/kg，共30天。存活30天后，海马CA1神经元损伤的程度进行了组织学评估。与对照组（8%存活率）相比，缺血后短时间轻度低温联合茶氨酸治疗显著增加（分别为67%和72%），表明短时间轻度低温联合PPF或茶氨酸对缺血性神经元损伤具有持续的有益作用。少

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