NADPH oxidase inhibition improves neurological outcomes in surgically-induced brain injury
NADPH oxidase inhibition improves neurological outcomes in surgically-induced brain injury
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DOI：
10.1016/j.neulet.2006.12.055
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发表时间：
2007-03-13
影响因子：
2.5
通讯作者：
Tang, Jiping
中科院分区：
文献类型：
--
作者：
Lo, Wendy;Bravo, Thomas;Tang, Jiping
神经外科手术可通过多种方式导致脑损伤，包括直接创伤、出血、牵开器拉伸和电灼。这种手术引起的脑损伤（SBI）可能会导致术后并发症，例如脑水肿。通过创建 SBI 小鼠模型，我们使用缺乏 NADPH 氧化酶 gp91(phox) 亚基 (gp91(phox) KO) 和 NADPH 氧化酶特异性抑制剂夹竹桃麻素的转基因小鼠，测试了 NADPH 氧化酶（一种重要的活性氧产生酶）是否参与 SBI。在 SBI 后 24 小时评估 gp91(phox) KO 和野生型同窝仔鼠的神经功能和脑水肿，分为 SBI 组和假手术组。或者，将小鼠分为媒介物治疗组和罗布麻宁治疗组（5 mg/kg，在 SBI 前 30 分钟腹腔注射）。在 SBI 后 3 小时和 24 小时测量脂质过氧化 (LPO) 指示的氧化应激。 gp91(phox) KO 小鼠（而非夹竹桃麻素治疗的小鼠）表现出神经系统评分显着改善。 SBI后gp91(phox) KO组和野生型组均观察到脑水肿；然而，这两组之间没有显着差异。脑水肿也不受罗布麻宁预处理的影响。与假手术组相比，SBI 组中 gp91(phox) KO 和野生型组的 LPO 水平均显着升高。尽管没有统计学意义，但与野生型组相比，gp91(phox) KO 动物中 LPO 减弱的趋势被注意到。通过罗布麻宁预处理，LPO 水平在 SBI 后 3 小时显着降低，但在 SBI 后 24 小时没有显着降低。这些结果表明，慢性和急性抑制 NADPH 氧化酶活性并不能减轻 SBI 后的脑水肿。然而，长期抑制 NADPH 氧化酶可改善 SBI 后的神经功能。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Neurosurgical procedures can result in brain injury by various means including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause post-operative complications such as brain edema. By creating a mouse model of SBI, we tested whether NADPH oxidase, an important reactive oxygen species producing enzyme, is involved in SBI using transgenic mice lacking gp91(phox) subunit of NADPH oxidase (gp91(phox) KO) and apocynin, a specific inhibitor of NADPH oxiclase. Neurological function and brain edema were evaluated at 24 It post-SBI in gp91(phox) KO and wild-type littermates grouped into SBI and sham-surgery groups. Alternatively, mice were grouped into vehicle- and apocynin-treated (5 mg/kg, i.p. 30 min before SBI) groups. Oxidative stress indicated by lipid peroxidation (LPO) was measured at 3 and 24 h post-SBI. The gp91(phox) KO mice, but not the apocynin-treated mice showed significantly improved neurological scores. Brain edema was observed in both gp91(phox) KO and wild-type groups after SBI; however, there was no significant difference between these two groups. Brain edema was also not affected by apocynin-pretreatment. LPO levels were significantly higher in SBI group in both gp91(phox) KO and wild-type groups as compared to sham group. A trend, although without statistical significance, was noted towards attenuation of LPO in the gp91(phox) KO animals as compared to wild-type group. LPO levels were significantly attenuated at 3 h post-SBI by apocynin-pretreatment but not at 24 h post-SBI. These results suggest that chronic and acute inhibition of NADPH oxidase activity does not reduce brain edema after SBI. Long-term inhibition of NADPH oxidase, however improves neurological functions after SBI. (c) 2006 Elsevier Ireland Ltd. All rights reserved.