crocin and Brain-Edema

Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe

Topics: Antioxidants; Brain Edema; Brain Injuries; Carotenoids; Cerebral Hemorrhage; Ferroptosis; Humans; Neurons; NF-E2-Related Factor 2; Oxidative Stress; Superoxide Dismutase

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that is associated with high morbidity and mortality. However, up to now, there are no effective prevention methods or specific therapies to improve its clinical outcomes. Herein, we explore preliminarily the efficacy of crocin, a carotenoid extracted from the stigma of saffron known for its anti-oxidation and free radical scavenging activities, in a mouse ICH model induced with collagenase infusion. Crocin or saline was administrated 6 h after ICH and then every 12 h for up to 7 days. Neurological scores were examined on days 1, 3, and 7 after ICH. Mice were sacrificed after1, 3, and 7 days of crocin treatment for examination of histology and immunohistochemistry. The results showed that oral administration of crocin attenuated the neurological deficits and reduced the myelin loss, neuron degeneration, iron deposition, reactive oxygen species (ROS) production and heme oxygenase-1 (HO-1) expression in the early stage of ICH, making it potential to be an ideal candidate for medical therapy of ICH in clinic.

Topics: Animals; Antioxidants; Brain; Brain Edema; Carotenoids; Cerebral Hemorrhage; Collagenases; Disease Models, Animal; Heme Oxygenase-1; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Nervous System Diseases; Reactive Oxygen Species; Stroke

A clear relationship exists between oxidative stress and disruption of blood-brain barrier (BBB) during cerebral ischemia, in which aging may exacerbate the extent of leakage. Here, we aim to examine the potential role of a water-soluble carotenoid-based antioxidant crocin on BBB damage in aged rats following cerebral ischemia.. A two months oral administration of crocin was applied to 24-month-old rats followed by an induction of brain ischemia by middle cerebral artery occlusion (MCAO). Brain infarction volume, water content, and neurological behavior assessments were measured in these animals at 24 hours after MCAO as compared to vehicle-treated controls. Evans blue dye extravasation assay was used to evaluate the BBB integrity. The levels of tight junction proteins, oxidative stress, and MMP (matrix metalloproteinases) activities were also determined in the ipsilateral brains of the MCAO-treated rats.. MCAO-induced brain injury was alleviated by the pretreatment of crocin. Crocin-treated animals also showed the preserved BBB function in the presence of ischemic injury. The loss of tight junction proteins and enhanced NADPH oxidase in the ipsilateral brains of the MCAO-treated rats were both reduced by crocin. Finally, the induction of MMP-2 and MMP-9 by cerebral ischemia was partially blocked by crocin in aged rats.. These findings indicate that crocin or related antioxidants may protect against cerebral ischemia of elderly patients by maintaining the integrity of BBB in aged rats, an effect likely through repressing the activation of matrix metalloproteinase pathway.

Topics: Actins; Analysis of Variance; Animals; Blood-Brain Barrier; Brain Edema; Brain Injuries; Carotenoids; Claudin-5; Disease Models, Animal; Free Radical Scavengers; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; NADPH Oxidases; Neurologic Examination; Rats; RNA, Messenger; Zonula Occludens-1 Protein

This study investigated the protective effects and mechanisms of crocin, an extract of saffron, on brain damage after traumatic brain injury (TBI) in mice. C57BL/6 mice were subjected to controlled cortical impact (CCI)-induced TBI. Pretreatment with crocin (20mg/kg) had protective effects against TBI, demonstrated by improved neurological severity score (NSS) and brain edema, decreased microglial activation and release of several pro-inflammatory cytokines, and decreased cell apoptosis. TBI activated Notch signaling, as shown by upregulated levels of Notch intracellular domain (NICD) and Hes1 mRNA, and pretreatment with crocin further increased Notch activation. However, pretreatment with DAPT (100mg/kg), a gamma-secretase inhibitor, significantly suppressed crocin-induced activation of Notch signaling and attenuated the ability of crocin to protect mice against TBI-induced inflammation and apoptosis. Therefore, these results suggest that crocin has neuroprotective effects against TBI in mice, and these effects are at least partially dependent on activation of Notch signaling.

Topics: Animals; Apoptosis; Brain Edema; Brain Injuries; Carotenoids; Inflammation; Male; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Receptors, Notch; Signal Transduction

Crocin is a water-soluble carotenoid isolated from the Crocus sativus L (saffron) stigma. It has previously been reported that it has protective effects against renal, cardiac, and global cerebral ischemic injury. However its therapeutic effects remain to be clarified regarding ischemic reperfusion injuries, brain edema, and activity of antioxidant enzymes in a transient model of focal cerebral ischemia.. Transient focal cerebral ischemia was induced by 60-minute middle cerebral artery occlusion (MCAO), followed by 23-hour reperfusion. Crocin at doses of 15, 30, 60, and 120 mg/kg intraperitoneally were injected at the start of ischemia. Infarct volume and neurologic outcome were evaluated 24 hours after MCAO. For the therapeutic time window measurement, crocin (60 mg/kg) was given 1, 3, and 6 hours after ischemia; 24 hours later brain edema and antioxidant enzyme activity were assessed.. The results indicated that treatment with crocin at doses of 30, 60, and 120 mg/kg significantly decreased infarct volume by 64%, 74%, and 73%, respectively. Administration of crocin (60 mg/kg) 1 hour before, at the start, or 1 hour after ischemia reduced brain edema by 48%, 52%, and 51%, respectively. Moreover, crocin (60 mg/kg) significantly reduced malondialdehyde (MDA) content and increased activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the ischemic cortex (P< .001).. Our findings indicate that crocin has protective effects against ischemic reperfusion injury and cerebral edema in a rat model of stroke. These effects of crocin may have been exerted primarily by suppression of the production of free radicals and increased antioxidant enzyme activity.

Topics: Animals; Antioxidants; Behavior, Animal; Body Water; Brain; Brain Edema; Brain Ischemia; Carotenoids; Cerebral Infarction; Cerebrovascular Circulation; Dose-Response Relationship, Drug; Glutathione Peroxidase; Male; Malondialdehyde; Rats; Rats, Wistar; Stroke; Superoxide Dismutase; Treatment Outcome

This paper studied the effects of crocin, a pharmacologically active component of Crocus sativus L., on ischemia/reperfusion (I/R) injury in mice cerebral microvessels. Transient global cerebral ischemia (20 min), followed by 24 h of reperfusion, significantly promoted the generation of nitric oxide (NO) and malondialdehyde (MDA) in cortical microvascular homogenates, as well as markedly reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and promoted the activity of nitric oxide synthase (NOs). Reperfusion for 24 h led to serous edema with substantial microvilli loss, vacuolation, membrane damage and mitochondrial injuries in cortical microvascular endothelial cells (CMEC). Furthermore, enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and decreased expression of matrix metalloproteinase-9 (MMP-9) were detected in cortical microvessels after I (20 min)/R (24 h). Reperfusion for 24 h also induced membrane (functional) G protein-coupled receptor kinase 2 (GRK2) expression, while it reduced cytosol GRK2 expression. Pretreatment with crocin markedly inhibited oxidizing reactions and modulated the ultrastructure of CMEC in mice with 20 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion in vivo. Furthermore, crocin inhibited GRK2 translocation from the cytosol to the membrane and reduced ERK1/2 phosphorylation and MMP-9 expression in cortical microvessels. We propose that crocin protects the brain against excessive oxidative stress and constitutes a potential therapeutic candidate in transient global cerebral ischemia.

Topics: Animals; beta-Adrenergic Receptor Kinases; Blood Vessels; Brain Edema; Brain Ischemia; Carotenoids; Cerebral Cortex; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; G-Protein-Coupled Receptor Kinase 2; Glutathione Peroxidase; Male; Malondialdehyde; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Microcirculation; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Phosphorylation; Reperfusion Injury; Subcellular Fractions; Superoxide Dismutase; Tissue Distribution