crocin and Brain-Injuries

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

Hypoxic-ischemic encephalopathy (HIE) is a serious medical situation at labor which leads to severe brain damage. Hypothermia therapy is the standard treatment for infants with HIE, but the efficacy is limited. Combination treatments are considered to enhance the efficacy of hypothermia. Crocin is an extract from saffron which has anti-inflammatory, anti-oxidant, and neuroprotective properties. The present study sought to investigate whether crocin could act as a combined treatment with hypothermia in a mouse model of HIE. C57BL/6J mice at post-natal day 7 were subjected to left common carotid artery ligation, followed by treatment of crocin (10 mg/kg) and hypothermia, either alone or in combination. Brain edema and tissue infarct were measured to evaluate brain damage. Mediators involved in inflammatory response and oxidative stress were measured. Neurological severity score test was performed to evaluate the functional outcome. Results show that crocin treatment alone could reduce inflammation and brain damage after hypoxia-ischemia. Combined treatment of crocin and hypothermia exerted enhanced therapeutic effect compared with single treatment, resulting in significantly less brain damage, reduced inflammatory and oxidative responses, and improved functional outcome. Together, these data suggest that crocin plays a beneficial effect in the mouse model of HIE. It could also enhance the neuroprotective effect of hypothermia and might be considered as a combination therapeutic treatment with hypothermia in HIE.

Topics: Animals; Animals, Newborn; Brain Injuries; Carotenoids; Combined Modality Therapy; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Mice; Mice, Inbred C57BL; Neuroprotective Agents

Owing to its lipophilic property, carbon tetrachloride (CCl

Topics: Animals; Brain; Brain Injuries; Carbon Tetrachloride; Carotenoids; Male; Neuroprotective Agents; Rats; Rats, Wistar; Reference Standards

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