RRC ID 43810
著者 Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A, Ohto T, Kita Y, Nakamura M, Suzuki S, Mochizuki M, Shimizu T, Chung UI, Sasaki N.
タイトル Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage.
ジャーナル J Transl Med
Abstract 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.
巻・号 10
ページ 80
公開日 2012-4-30
DOI 10.1186/1479-5876-10-80
PII 1479-5876-10-80
PMID 22546323
PMC PMC3422174
MeSH Animals Cells, Cultured Disease Models, Animal Hemolysis / drug effects Humans Inflammation / blood Inflammation / complications Inflammation / drug therapy* Inflammation / pathology Lipid Peroxidation / drug effects Male Mice NF-kappa B / metabolism Oxidative Stress* / drug effects Rabbits Rats Rats, Sprague-Dawley Rats, Wistar Reactive Oxygen Species / metabolism Signal Transduction / drug effects Subarachnoid Hemorrhage / blood Subarachnoid Hemorrhage / chemically induced Subarachnoid Hemorrhage / complications* Subarachnoid Hemorrhage / drug therapy Trehalose / pharmacology Trehalose / therapeutic use* Vasospasm, Intracranial / blood Vasospasm, Intracranial / drug therapy* Vasospasm, Intracranial / etiology* Vasospasm, Intracranial / pathology
IF 4.124
引用数 64
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)