Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage

Journal of Translational Medicine

Nobuo Sasaki⁴  Ung-il Chung²  Takao Shimizu⁵  Manabu Mochizuki⁴  Shigeki Suzuki³  Motonao Nakamura⁵  Yoshihiro Kita⁵  Takayo Ohto⁵  Ayano Fujisawa²  Yuko Kayasuga-Kariya²  Fumiko Yano¹  Kensuke Karatsu⁴  Nobuyuki Shimohata¹  Ryosuke Echigo⁴ 

[1] Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-8656, Japan;NEXT21 K.K., 3-38-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan;Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan;Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

关键词: Oxidative stress;    Inflammatory response;    Cerebral vasospasm;    Subarachnoid hemorrhage;    Trehalose;   

Others  :  1206001
DOI  :  10.1186/1479-5876-10-80

 received in 2011-12-15, accepted in 2012-04-30,  发布年份 2012

【 摘 要 】

Background

Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo.

Methods

Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed.

Results

When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only a moderate effect. When the rat femoral arteries exposed to blood were investigated for 20 days, histological analysis revealed that trehalose suppressed vasospasm, inflammatory response, and lipid peroxidation.

Conclusions

These data suggest that trehalose has suppressive effects on several pathological events after SAH, including vasospasm, inflammatory responses, and lipid peroxidation. Trehalose may be a new therapeutic approach for treatment of complications after SAH.

【 授权许可】

   
2012 Echigo et al.; licensee BioMed Central Ltd.

【 图 表 】

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