astaxanthine and Brain-Edema

The aim of the study was to investigate the effect of astaxanthin and its possible mechanisms on acute cerebral infarction (ACI) in rat model. Male Sprague Dawley rats were randomly divided into sham group, model group, and astaxanthin-treated groups (20, 40, and 80 mg/kg). Neurological examination, the ratio of cerebral edema, and histopathology changes were assessed. Moreover, some oxidative stress markers were obtained for biochemical analysis, and the expression of neurotrophic factors gene was detected by real-time polymerase chain reaction (RT-PCR) method. The results showed that treatment with astaxanthin notably reduced neurological deficit scores and the ratio of cerebral edema compared with the model group. Meanwhile, astaxanthin increased the activity of catalase, superoxide dismutase, and glutathioneperoxidase as well as decreased the content of malondialdehyde in brain tissue. RT-PCR results showed that the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNA were increased with astaxanthin treatment. The results indicated that astaxanthin could ameliorate ACI followed by suppressing oxidative stress and upregulating the expression of BDNF and NGF mRNA.

Topics: Acute Disease; Animals; Antioxidants; Brain; Brain Edema; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; Motor Activity; Nerve Growth Factor; Neuroprotective Agents; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction; Up-Regulation; Xanthophylls

Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI).. Our results showed that, following CCI, treatment with astaxanthin compared to vehicle ameliorated neurologic dysfunctions after day 3 and alleviated cerebral edema and Evans blue extravasation at 24 h (p < 0.05). Astaxanthin treatment decreased AQP4 and NKCC1 mRNA levels in a dose-dependent manner at 24 h. AQP4 and NKCC1 protein expressions in the peri-contusional cortex were significantly reduced by astaxanthin at 24 h (p < 0.05). Furthermore, we also found that bumetanide (BU), an inhibitor of NKCC1, inhibited trauma-induced AQP4 upregulation (p < 0.05).. Our data suggest that astaxanthin reduces TBI-related injury in brain tissue by ameliorating AQP4/NKCC1-mediated cerebral edema and that NKCC1 contributes to the upregulation of AQP4 after TBI.

Topics: Animals; Aquaporin 4; Brain; Brain Edema; Brain Injuries, Traumatic; Bumetanide; Capillary Permeability; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Male; Mice, Inbred C57BL; Neuroprotective Agents; Random Allocation; RNA, Messenger; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2; Xanthophylls

We have previously shown that astaxanthin (ATX) reduces the blood-brain barrier (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage (SAH) insults. However, the underlying mechanisms remain unclear. It is known that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we investigated whether ATX could ameliorate MMP-9 activation and expression in a rat model of SAH. A total of 144 rats were randomly divided into the following groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous blood into the prechiasmatic cistern. ATX (20 μl of 0.1 mmol) or vehicle was administered intracerebroventricularly 30 min after SAH induction. Mortality, neurological function, brain edema and blood-brain barrier (BBB) permeability were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were used to analyze MMP-9 expression and activity in brain samples. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were also evaluated at 24h. Our data indicated that ATX could significantly reduce the expression and activity of MMP-9, leading to the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL-positive cells at 24h but not 72 h after SAH. The ATX-mediated down-regulation of MMP-9 was correlated with the decreased levels of IL-1β, TNF-α, oxidative stress, activated microglia and infiltrating neutrophils. These results suggest that the neurovascular protection of ATX in SAH is partly associated with the inhibition of MMP-9 expression and activity.

Topics: Analysis of Variance; Animals; Blood-Retinal Barrier; Brain; Brain Edema; Capillary Permeability; Disease Models, Animal; Gene Expression Regulation, Enzymologic; In Situ Nick-End Labeling; Male; Malondialdehyde; Matrix Metalloproteinase 9; Neurologic Examination; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Time Factors; Xanthophylls

Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model.. Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1β, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity.. Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration.. These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Cell Death; Disease Models, Animal; Interleukin-1beta; Male; Neuritis; Neuroprotective Agents; NF-kappa B; Optic Chiasm; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha; Xanthophylls