title: Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage.
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.
authors.affiliation: 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.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Echigo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimohata
authors.forename: Kensuke
authors.initials: K
authors.lastname: Karatsu
authors.forename: Fumiko
authors.initials: F
authors.lastname: Yano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kayasuga-Kariya
authors.forename: Ayano
authors.initials: A
authors.lastname: Fujisawa
authors.forename: Takayo
authors.initials: T
authors.lastname: Ohto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kita
authors.forename: Motonao
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Suzuki
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Ung-Il
authors.initials: UI
authors.lastname: Chung
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D014199:Trehalose / Q000494:pharmacology / Q000627:therapeutic use*; D020301:Vasospasm, Intracranial / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014199:Trehalose