astaxanthine and Brain-Ischemia

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

Topics: Animals; Antioxidants; Brain Injuries; Brain Ischemia; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Stroke; Xanthophylls

Acute cerebral infarction (ACI) is susceptible to cause disability or death of people. Astaxanthin (ATX) possesses the protective effect of organ injury. Therefore, the study was to explore the potential mechanism of protective effect with ATX on ACI.. 30 SD rats were divided into Sham, ACI, and ATX groups. The rats in the ATX group were pretreated with ATX by gavage for three days before surgery, while the rats in the other two groups were pretreated with saline. The model of ACI was established by thread embolization. 24 h after the operation, the neurological function was scored, and cerebral infarct area and pathological morphology of brains were measured; the edema of the brain was detected by dry/wet method; Western blot was applied to measure the translocation of Nrf-2 and the protein expression of HO-1, Bax and BCL-2; Brain cell apoptosis was assessed through TUNEL; ELISA was used to detect the oxidative stress factors of catalase (CAT) superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA), and the inflammatory factors of TNF-α, IL-1β, IL-6.. Compared with the ACI group, ATX pretreatment can significantly improve neurological function; reduce the edema index of the brain, cerebral infarct area, cerebral pathological damage and apoptosis of brain cells. Moreover, ATX also can increase the protein expression of nuclear Nrf-2, HO-1, BCL-2, CAT, SOD, and GPX by decreasing the content of TNF-α, IL-1β, IL-6, MDA, Bax and cytosolic Nrf-2.. ATX might have a protective effect of acute cerebral infarction, and the mechanism is probably associated with suppressing oxidative stress, inflammation, and apoptosis by activating Nrf-2/HO-1signalling.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Rats; Rats, Sprague-Dawley; Signal Transduction; Xanthophylls

Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28days. The results showed that ATX treatment ameliorated learning and memory deficits after repeated cerebral IR. ATX administration rescued the number of surviving pyramidal neurons in the CA1 and CA3 regions. The concentration of malondialdehyde was decreased, and the levels of reduced glutathione and superoxide dismutase in the hippocampus were increased. Electron microphotography revealed that damage to the ultrastructure of neurons was also reduced by ATX administration. In addition, the expression levels of Cytochrome C (Cyt C), cleaved Caspase-3 and Bax were lower and the expression of Bcl-2 was higher compared to control IR mice. Our findings demonstrate that ATX is able to suppresse learning and memory impairment caused by repeated cerebral IR and that this effect is associated with attenuation of oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Cytochromes c; Dementia, Vascular; Disease Models, Animal; Glutathione; Hippocampus; Learning; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Oxidative Stress; Reperfusion; Reperfusion Injury; Superoxide Dismutase; Xanthophylls

Astaxanthin, a natural antioxidant carotenoid, has been shown to reduce cerebral ischemic injury in rodents. However, there have not been any studies specifically addressing whether preventive administration of astaxanthin can protect against cerebral ischemia. The purpose of this study was to examine whether pretreatment of astaxanthin can protect against ischemic injuries in the adult rats. The rats were pre-administered intragastrically with astaxanthin for seven days (once a day), and middle cerebral artery occlusion was performed at 1h after the final administration. It was found that astaxanthin prevented neurological deficits and reduced cerebral infarction volume. To evaluate the mechanisms underlying this protection, brain tissues were assayed for free radical damage, antioxidant gene expression, cell apoptosis and regeneration. The results showed that the mechanisms involved suppression of reactive oxygen species, activation of antioxidant defense pathway, and inhibition of apoptosis as well as promotion of neural regeneration. Astaxanthin did not alter body weights and the protective effect was found to be dose-dependent. Collectively, our data suggest that pretreatment of astaxanthin can protect against ischemia-related damages in brain tissue through multiple mechanisms, hinting that astaxanthin may have significant protective effects for patients vulnerable or prone to ischemic events.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Cell Death; Male; Neuroprotective Agents; Rats, Sprague-Dawley; Reactive Oxygen Species; Stroke; Xanthophylls

Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

Topics: Aconitate Hydratase; Animals; Behavior, Animal; Brain Injuries; Brain Ischemia; Cerebrovascular Circulation; Crustacea; Cytochromes c; Diet; Glutamic Acid; Humans; In Situ Nick-End Labeling; Lipid Peroxidation; Male; Molecular Structure; Motor Activity; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Xanthophylls