Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase
Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase
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DOI：
10.1016/j.brainres.2009.08.096
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发表时间：
2009-11
期刊：
影响因子：
2.9
通讯作者：
Satoshi Yamashita;Takao Hirata;Y. Mizukami;Y. Cui;S. Fukuda;K. Ishida;M. Matsumoto;T. Sakabe
中科院分区：
文献类型：
--
作者：
Satoshi Yamashita;Takao Hirata;Y. Mizukami;Y. Cui;S. Fukuda;K. Ishida;M. Matsumoto;T. Sakabe
我们以前报道过高压氧预处理（HBO; 100%O23.5-atomsphere absolute（ATA），1 h/d，共5 d）对大鼠短暂性前脑缺血（8 min）具有神经保护作用，其机制可能与神经营养因子受体和炎症免疫系统相关蛋白的合成有关。最近的报道表明HBO诱导的神经保护作用与脑源性神经营养因子及其下游事件有关，包括抑制p38丝裂原活化蛋白激酶（p38）的活化。在本研究中，我们首先进行了剂量比较，（1，2和3.5 ATA）HBO诱导的神经保护作用，然后研究10 mg/kg茴香霉素的药理学修饰（蛋白质合成抑制剂和p38的强效激活剂）和200 μg/kg SB 203580（p38抑制剂），分别于每次3. 5ATA-HBO治疗前60和30 min腹腔注射。观察到3.5 ATA-HBO对海马CA 1神经元的最显著保护作用（存活神经元：69% [62-73%] vs.未处理：3.9% [2-8%]，1 ATA：8.8% [0-26%]，2 ATA-HBO：46% [22-62%]（中位数[范围]）（缺血后7天）。茴香霉素消除了神经保护作用（存活神经元：1.2% [0-7%]）。SB 203580在茴香霉素给药和HBO治疗之间给药时，恢复了神经保护作用（存活神经元：52% [37-62%]）。再灌注10分钟时，3.5 ATA-HBO组的磷酸化p38水平显著降低（为假手术组的32% [12-53%]）。SB 203580 100和200 μg/kg单次预处理分别产生与2和3.5 ATA-HBO预处理相似的神经保护作用（39% [25-51%]和59% [50-72%]）。它的结论是，抑制p38磷酸化在HBO诱导的神经保护中起着关键作用，并与p38抑制剂（SB 203580）预处理可以提供类似的神经保护。
We previously reported in rats that preconditioning with hyperbaric oxygen (HBO; 100% O23.5-atomsphere absolute (ATA), 1 h/day for 5 days) provided neuroprotection against transient (8 min) forebrain ischemia possibly through protein synthesis relevant to neurotrophin receptor and inflammatory–immune system. A recent report suggested that HBO-induced neuroprotection is relevant to brain derived neurotrophic factor and its downstream event involving suppression of p38 mitogen activated protein kinase (p38) activation. In the present study, we first performed a dose comparison (1, 2, and 3.5 ATA) of HBO-induced neuroprotection and then investigated pharmacological modification by 10 mg/kg anisomycin (a protein synthesis inhibitor and potent activator for p38) and 200 μg/kg SB203580 (a p38 inhibitor), which were given intraperitoneally 60 and 30 min before every 3.5 ATA-HBO treatment, respectively. Most prominent protective effect on hippocampal CA1 neurons was observed with 3.5 ATA-HBO (survived neurons: 69% [62–73%] vs. untreated: 3.9% [2–8%], 1 ATA: 8.8% [0–26%], 2 ATA-HBO: 46% [22–62%] (median [range]) (7 days after ischemia). Anisomycin abolished a neuroprotective effect (survived neuron: 1.2% [0–7%]). SB203580, when given between administration of anisomycin and HBO treatment, resumed a neuroprotective effect (survived neuron: 52% [37–62%]). The level of phosphorylated p38 at 10-min reperfusion was significantly decreased in 3.5 ATA-HBO group (32% [12–53%] of sham). Single pretreatment with 100 and 200 μg/kg of SB203580 exerted a similar neuroprotective effect (39% [25–51%] and 59% [50–72%]) to 2 and 3.5 ATA-HBO preconditioning, respectively. It is concluded that suppression of p38 phosphorylation plays a key role in HBO-induced neuroprotection and that pretreatment with a p38 inhibitor (SB203580) can provide similar neuroprotection.