3′-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein（an active ingredient of the kudzu vine root）. It has been shown to have a protective effect on cerebral ischemia/reperfus...3′-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein（an active ingredient of the kudzu vine root）. It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3′-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3′-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3′-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3′-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.展开更多
Mitochondria play an important role in neuronal apoptosis caused by cerebral ischemia, and the role is mediated by the expression of mitochondrial proteins. This study investigated the involvement of mitochondrial pro...Mitochondria play an important role in neuronal apoptosis caused by cerebral ischemia, and the role is mediated by the expression of mitochondrial proteins. This study investigated the involvement of mitochondrial proteins in hippocampal cell apoptosis after transient cerebral ischemia-reperfusion injury in aged rats using a comparative proteomics strategy. Our exper-imental results show that the aged rat brain is sensitive to ischemia-reperfusion injury and that transient ischemia led to cell apoptosis in the hippocampus and changes in memory and cognition of aged rats. Differential proteomics analysis suggested that this phenomenon may be mediated by mitochondrial proteins associated with energy metabolism and apoptosis in aged rats. This study provides potential drug targets for the treatment of transient cerebral isch-emia-reperfusion injury.展开更多
Mitochondria play a kay role in various cell processes including ATP production, Ca^2＋ homeostasis, reactive oxygen species （ROS） generation, and apoptosis. The selective removal of impaired mitochondria by autopha...Mitochondria play a kay role in various cell processes including ATP production, Ca^2＋ homeostasis, reactive oxygen species （ROS） generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insuf- ficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.展开更多
Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of...Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow （rCBF, using ^99rnTc tracer technique ）, the brain water content （specific gravimetric method）, PAFR （3H-labelled PAF assay）, the respiratory control rate （RCR）, the phosphorus-oxygen （P/O） ratio of mitochondrial respiration （Clark oxygen electrode）, mitochonddal permeability transition （MPT） pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups （the ischemia group vs the sham group, and the ischemia group vs the GB group）. Results There were high affinity and low affinity sites for PAFR on the tree threws＇ brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly （respectively, P〈0.01 and P〈0.05）, but the water content increased （P〈0.01） in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB （5 mg/kg i.v.） 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated （P〈0.01） at 24h after cerebral ischemia. There were significant differences between the ischemJa group and sham group （P〈0.01）. In GB treated isolated neurons＇ mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. Conclusions The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.展开更多
基金supported by the National Natural Science Foundation of China,No.81160399,81560583the Science and Technology Landing Project of China,No.KJLD13085the Science and Technology Project of the Education Department of Jiangxi Province of China,No.GJJ12560
文摘3′-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein（an active ingredient of the kudzu vine root）. It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3′-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3′-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3′-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3′-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.
基金supported by a grant from Ministry of Science and Technology of Qingdao City,No.10-3-4-7-8-JCH
文摘Mitochondria play an important role in neuronal apoptosis caused by cerebral ischemia, and the role is mediated by the expression of mitochondrial proteins. This study investigated the involvement of mitochondrial proteins in hippocampal cell apoptosis after transient cerebral ischemia-reperfusion injury in aged rats using a comparative proteomics strategy. Our exper-imental results show that the aged rat brain is sensitive to ischemia-reperfusion injury and that transient ischemia led to cell apoptosis in the hippocampus and changes in memory and cognition of aged rats. Differential proteomics analysis suggested that this phenomenon may be mediated by mitochondrial proteins associated with energy metabolism and apoptosis in aged rats. This study provides potential drug targets for the treatment of transient cerebral isch-emia-reperfusion injury.
基金This work was funded by the Faculty Research Grant of Hong Kong Baptist University （FRG2/15-16/022） and the Guandong Natural Science Foundation （2014A030313766 and 2016A030313008）.
文摘Mitochondria play a kay role in various cell processes including ATP production, Ca^2＋ homeostasis, reactive oxygen species （ROS） generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insuf- ficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.
基金the grants from Specialized Research Fund for the Doctoral Program of Higher Education(No.20050678008)National Natural Science Foundation of China (No.3066005).
文摘Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow （rCBF, using ^99rnTc tracer technique ）, the brain water content （specific gravimetric method）, PAFR （3H-labelled PAF assay）, the respiratory control rate （RCR）, the phosphorus-oxygen （P/O） ratio of mitochondrial respiration （Clark oxygen electrode）, mitochonddal permeability transition （MPT） pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups （the ischemia group vs the sham group, and the ischemia group vs the GB group）. Results There were high affinity and low affinity sites for PAFR on the tree threws＇ brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly （respectively, P〈0.01 and P〈0.05）, but the water content increased （P〈0.01） in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB （5 mg/kg i.v.） 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated （P〈0.01） at 24h after cerebral ischemia. There were significant differences between the ischemJa group and sham group （P〈0.01）. In GB treated isolated neurons＇ mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. Conclusions The activation of the PAFR may play an important role in the inhibition of the mitochondrial respiration and the induction of neuronal damage after cerebral thrombosis; however, GB possesses neuroprotective effects by improving mitochondrial metabolism.
