Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase

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• 作者：Satoshi Yamashita ; Takao Hirata ; Yoichi Mizukami ; Ying Jun Cui ; Shiro Fukuda ; Kazuyoshi Ishida ; Mishiya Matsumoto ; Takefumi Sakabe
• 关键词：Hyperbaric oxygen ; Hippocampal CA1 ; Forebrain ischemia ; Neuroprotection ; p38 mitogen activated protein kinase
• 刊名：Brain Research
• 出版年：2009
• 出版时间：16 November 2009
• 年：2009
• 卷：1301
• 期：Complete
• 页码：171-179
• 全文大小：532 K

文摘

We previously reported in rats that preconditioning with hyperbaric oxygen (HBO; 100 % O₂ 3.5-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.