crocin and Brain-Ischemia

Although the memory- improving effect of crocin has been suggested by previous evidences, the association between this effect and hippocampal acetylcholine (Ach) level and apoptosis is not well investigated. This study aimed to determine the protective effects of crocin on memory, hippocampal Ach level, and apoptosis in a rat model of cerebral ischemia. Male Wistar rats were divided into sham group received saline, and other 3 groups underwent 4-vessel occlusion brain ischemia (4VOI), received oral administration of either saline or crocin in doses of 30 mg/day and 60 mg/day for 7 days. Outcomes were memory, determined by radial eight-arm maze (RAM) task and Morris water maze (MWM) test, Ach release in the dorsal hippocampus (evaluated by microdialysis-HPLC) and apoptosis (investigated by TUNEL assay). 4VOI impaired memory reduced dorsal hippocampus Ach level, and induced apoptosis. Crocin, significantly improved the memory (F = 343.20; P < 0.001 for RAM error choices and F = 182.5; P < 0.0001 for MWM), increased Ach level (F = 115.1; P < 0.001) and prevented hippocampal neuronal apoptosis (W = 183.50; P < 0.001) as compared statistically by ANOVA test. Crocin can be suggested as a promising therapy for ischemic cerebrovascular accidents by its memory preserving, Ach-increasing, and neuroprotective effects.

Topics: Acetylcholine; Animals; Apoptosis; Brain Ischemia; Carotenoids; Hippocampus; Male; Maze Learning; Memory; Memory Disorders; Neurons; Neuroprotective Agents; Rats; Rats, Wistar

To investigate the effects of crocin on proliferation and migration of endogenous neural stem cells and the Notch1 signalling pathway in rats after cerebral ischemia reperfusion.. SD rats were randomly divided into the sham operation group, model group and administration group (crocin). Middle cerebral artery occlusion (MCAO/R) was used to establish the focal cerebral ischemia reperfusion model in rat. After surgical treatment, the treatment group was treated with crocin. Quantitative polymerase chain reaction (qPCR) was used to detect the changes in the expression of Notch1, Bax and bcl-2 proteins in rat endogenous neural stem cells after cerebral ischemia reperfusion. ELISA was used to detect changes in inflammatory factors. Neural stem cells were cultured in vitro, which were divided into: the normal control group, the hypoglycaemic deprivation/reoxygenation group, hypoglycaemic deprivation/reoxygenation group with a low concentration of crocin, and hypoglycaemic deprivation/reoxygenation group with a high concentration of crocin. The cell proliferation assay detects cell activity. The cell migration assay tests the cell migration ability. And flow cytometry was used to determine cell apoptosis.. Compared with the sham group, the Notch1 signalling pathway was activated in the model group. The expression of Notch1 in the crocin group was increased compared to the model group. Crocin can inhibit the release of inflammatory factors. The results of our experiments showed that crocin could induce the proliferation and migration of neural stem cells and inhibit the apoptosis of neural stem cells in the hypoglycaemic/reoxygenation model group.. Crocin sufficiently promotes the proliferation and migration of neural stem cells and inhibits the apoptosis of these cells in rats after ischemia-reperfusion by manipulating the Notch signalling pathway.

Topics: Animals; Apoptosis; Brain Ischemia; Carotenoids; Cell Movement; Cell Proliferation; Female; Infarction, Middle Cerebral Artery; Neural Stem Cells; Rats; Rats, Sprague-Dawley; Receptor, Notch1; Signal Transduction

Cerebral ischemia reperfusion (IR) injury is a process in which oxidative and apoptotic mechanisms play a part. Neuroprotective agents to be found could work out well for the efficient and safe minimization of cerebral IR injury. Crocin is a strong antioxidant agent; however the influence of this agent on the experimental cerebral ischemia model has not been studied extensively and thus it is not well-known. The objective of our study was to investigate the antioxidant, antiapoptotic and protective effects of crocin on the global cerebral IR induced by four-vessel occlusion.. A total of 30 adult female Sprague-Dawley rats were equally and randomly separated into three groups as follows: sham, IR and IR+crocin (40mg/kg/day orally for 10days). 24h after electrocauterization of bilateral vertebral arteries, bilateral common carotid arteries were occluded for 30min and reperfused for 30min. Oxidative stress parameters (TAS, TOS, OSI), haematoxylin and eosin staining, caspase-3 and hypoxia-inducible factor-1 alpha (HIF-1α) expressions and TUNEL methods were investigated.. There was a significant difference between the IR and sham groups by means of OSI level, histopathological scoring, caspase-3, HIF-1α and TUNEL-positive cell parameters. We have also observed that pre-treatment with crocin reduced these parameter levels back to the baseline.. The data obtained from the present study suggest that crocin may exert antiapoptotic, antioxidant and protective effects in IR-mediated brain injury induced by four-vessel occlusion. To the best of our knowledge, this would be the first study to be conducted in this field.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Carotenoids; Cerebrovascular Circulation; Female; Rats; Rats, Sprague-Dawley; Reperfusion Injury

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