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

Abstract

BackgroundSubarachnoid 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.MethodsEnzyme 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.ResultsWhen 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.ConclusionsThese 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.

Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced in an AAV α-Synuclein Rat Model of Parkinson’s Disease

“…It has also been suggested to have antiinflammatory, anti-oxidative stress, and anti-apoptotic effects [34][35][36]. These roles, coupled with anti-aggregation properties and lack of toxicity, enhance the potential translational value of trehalose.…”

Characterization of spinal subarachnoid bleeding associated to graded traumatic spinal cord injury in the rat

“…Brain subarachnoid bleeding in humans and experimental animals, resulting from events such as ruptured aneurysms or brain injury, triggers inter-related pathomechanisms partially attributable to the release of toxic byproducts of hemoglobin degradation, [10][11][12] leading to irreversible brain damage and even death. Delayed ischemic neurological deficit is recognized as the most prominent complication of brain subarachnoid bleeding, 10,12 and has been associated to several mechanisms including vasospasms, 10 failure of blood flow autoregulation, 7 disruption of the blood-brain barrier, 12 edema, 12 microthrombosis, 13 inflammation 11 and oxidative stress, 10 among others.…”

“…Delayed ischemic neurological deficit is recognized as the most prominent complication of brain subarachnoid bleeding, 10,12 and has been associated to several mechanisms including vasospasms, 10 failure of blood flow autoregulation, 7 disruption of the blood-brain barrier, 12 edema, 12 microthrombosis, 13 inflammation 11 and oxidative stress, 10 among others. Conditions such as these can in turn lead to alterations in neuronal signal processing and transmission, 12 infarctions 6 and gliosis.…”

Hydrogen-Rich Saline Attenuated Subarachnoid Hemorrhage-Induced Early Brain Injury in Rats by Suppressing Inflammatory Response: Possible Involvement of NF-κB Pathway and NLRP3 Inflammasome

“…As another pivotal signaling pathway, NF-κB pathway has been deemed to play a dominating role in inflammation post-SAH, which could be activated due to excess ROS generation. Accumulating evidence demonstrated that many agents (recombinant osteopontin, urinary trypsin inhibitor, trehalose, progesterone, et al) alleviated inflammatory response after SAH, partially via inhibiting NF-κB inflammatory pathway [24][25][26][27]. NLRP3 inflammasome is another key component of inflammatory response.…”