PMID- 17274961 OWN - NLM STAT- MEDLINE DCOM- 20070521 LR - 20220409 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1138 DP - 2007 Mar 23 TI - Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. PG - 86-94 AB - 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. FAU - Zheng, Yong-Qiu AU - Zheng YQ AD - Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, 1, Xi Yuan yard Road, Haidian District, Beijing 100091, PR China. yongqiuzheng@sina.com FAU - Liu, Jian-Xun AU - Liu JX FAU - Wang, Jan-Nong AU - Wang JN FAU - Xu, Li AU - Xu L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061229 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 31C4KY9ESH (Nitric Oxide) RN - 36-88-4 (Carotenoids) RN - 4Y8F71G49Q (Malondialdehyde) RN - 877GWI46C2 (crocin) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.15 (GRK2 protein, mouse) RN - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases) RN - EC 2.7.11.16 (G-Protein-Coupled Receptor Kinase 2) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Blood Vessels/metabolism/pathology MH - Brain Edema/etiology/pathology MH - Brain Ischemia/metabolism/*pathology MH - Carotenoids/*pharmacology MH - Cerebral Cortex/*blood supply MH - Endothelial Cells/drug effects/ultrastructure MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - G-Protein-Coupled Receptor Kinase 2 MH - Glutathione Peroxidase/metabolism MH - Male MH - Malondialdehyde/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microcirculation MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase/metabolism MH - Oxidative Stress/*drug effects MH - Phosphorylation/drug effects MH - Reperfusion Injury/complications/metabolism/*pathology MH - Subcellular Fractions/metabolism MH - Superoxide Dismutase/metabolism MH - Tissue Distribution MH - beta-Adrenergic Receptor Kinases/metabolism EDAT- 2007/02/06 09:00 MHDA- 2007/05/22 09:00 CRDT- 2007/02/06 09:00 PHST- 2006/09/15 00:00 [received] PHST- 2006/12/17 00:00 [revised] PHST- 2006/12/20 00:00 [accepted] PHST- 2007/02/06 09:00 [pubmed] PHST- 2007/05/22 09:00 [medline] PHST- 2007/02/06 09:00 [entrez] AID - S0006-8993(06)03683-3 [pii] AID - 10.1016/j.brainres.2006.12.064 [doi] PST - ppublish SO - Brain Res. 2007 Mar 23;1138:86-94. doi: 10.1016/j.brainres.2006.12.064. Epub 2006 Dec 29.