Objective:To investigate the potential mechanisms of electroacupuncture(EA)to prevent ischemic stroke.Methods:The method of middle cerebral artery occlusion(MCAO)was employed to establish a rat model of ischemic strok...Objective:To investigate the potential mechanisms of electroacupuncture(EA)to prevent ischemic stroke.Methods:The method of middle cerebral artery occlusion(MCAO)was employed to establish a rat model of ischemic stroke.Seventy-eight Sprague-Dawley rats were divided into the sham group,MCAO+EA control(EC)group,and MCAO+EA(EA)group according to a random number table(n=26 per group).EA was applied to the acupoints of Baihui(DU 20)and Shenting(DU 24)5 min and 6 h,respectively after the onset of MCAO for 30 min.Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO.The neuroprotective effects of EA were evaluated by rota-rod test,neurological deficit scores and infarct volumes.Additionally,Nissl staining and immunostaining were performed to examine brain damage,rod formation,cellular apoptosis,and neuronal loss induced by ischemia.The activities of caspase-3,and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot.Results:Compared with the EC group,EA significantly improved neuromotor function and cognitive ability after ischemic stroke(P<0.05 or P<0.01).Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2(MAP2)degradation in the cortical penumbra area compared with the EC rats(P<0.01).Furthermore,Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage(P<0.05 or P<0.01).Additionally,brain damage(infarct volume and neuropathy),cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats(P<0.05 or P<0.01).Conclusion:EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin,a novel mechanism of EA therapy.展开更多
Since the first demonstration of sperm entry into the fertilized eggs of Mediterranean sea urchin Paracentrotus lividus by Hertwig(1876),enormous progress and insights have been made on this topic.However,the precise ...Since the first demonstration of sperm entry into the fertilized eggs of Mediterranean sea urchin Paracentrotus lividus by Hertwig(1876),enormous progress and insights have been made on this topic.However,the precise molecular mechanisms underlying fertilization are largely unknown.The two most dramatic changes taking place in the zygote immediately after fertilization are:(i) a sharp increase of intracellular Ca2+ that initiates at the sperm interaction site and traverses the egg cytoplasm as a wave,and(ii) the concomitant dynamic rearrangement of the actin cytoskeleton.Traditionally,this has been studied most extensively in the sea urchin eggs,but another echinoderm,starfish,whose eggs are much bigger and transparent,has facilitated experimental approaches using microinjection and fluorescent imaging methodologies.Thus in starfish,it has been shown that the sperm-induced Ca2+ increase in the fertilized egg can be recapitulated by several Ca2+ -evoking second messengers,namely inositol 1,4,5-trisphosphate(InsP3) ,cyclic ADP-ribose(cADPr) and nicotinic acid adenine dinucleotide phosphate(NAADP) ,which may play distinct roles in the generation and propagation of the Ca2+ waves.Interestingly,it has also been found that the dynamic rearrangement of the actin cytoskeleton in the fertilized eggs plays pivotal roles in guiding monospermic sperm entry and in the fine modulation of the intracellular Ca2+ signaling.As it is well known that Ca2+ regulates the structure of the actin cytoskeleton,our finding that Ca2+ signaling can be reciprocally affected by the state of the actin cytoskeleton raises an intriguing possibility that actin and Ca2+ signaling may form a'positive feedback loop'that accelerates the downstream events of fertilization.Perturbation of the cortical actin networks also inhibits cortical granules exocytosis.Polymerizing actin bundles also compose the'acrosome process,'a tubular structure protruding from the head of fertilizing sperm. Hence,actin,which is one of the most strictly conserved proteins in e展开更多
基金Supported by the National Natural Science Foundation of China(No.81804175 and 81803883)Natural Science Foundation of Fujian Province(No.2019J01497)+2 种基金Foundation of Fujian Key Laboratory of Rehabilitation Technology(No.KF2019006)Special Research Project of National Clinical Research Base of Traditional Chinese Medicine(No.JDZX2019040)Educational Research Project for Young and Middle-Aged Teachers of Education Bureau of Fujian Province(No.JT180216)。
文摘Objective:To investigate the potential mechanisms of electroacupuncture(EA)to prevent ischemic stroke.Methods:The method of middle cerebral artery occlusion(MCAO)was employed to establish a rat model of ischemic stroke.Seventy-eight Sprague-Dawley rats were divided into the sham group,MCAO+EA control(EC)group,and MCAO+EA(EA)group according to a random number table(n=26 per group).EA was applied to the acupoints of Baihui(DU 20)and Shenting(DU 24)5 min and 6 h,respectively after the onset of MCAO for 30 min.Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO.The neuroprotective effects of EA were evaluated by rota-rod test,neurological deficit scores and infarct volumes.Additionally,Nissl staining and immunostaining were performed to examine brain damage,rod formation,cellular apoptosis,and neuronal loss induced by ischemia.The activities of caspase-3,and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot.Results:Compared with the EC group,EA significantly improved neuromotor function and cognitive ability after ischemic stroke(P<0.05 or P<0.01).Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2(MAP2)degradation in the cortical penumbra area compared with the EC rats(P<0.01).Furthermore,Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage(P<0.05 or P<0.01).Additionally,brain damage(infarct volume and neuropathy),cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats(P<0.05 or P<0.01).Conclusion:EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin,a novel mechanism of EA therapy.
文摘Since the first demonstration of sperm entry into the fertilized eggs of Mediterranean sea urchin Paracentrotus lividus by Hertwig(1876),enormous progress and insights have been made on this topic.However,the precise molecular mechanisms underlying fertilization are largely unknown.The two most dramatic changes taking place in the zygote immediately after fertilization are:(i) a sharp increase of intracellular Ca2+ that initiates at the sperm interaction site and traverses the egg cytoplasm as a wave,and(ii) the concomitant dynamic rearrangement of the actin cytoskeleton.Traditionally,this has been studied most extensively in the sea urchin eggs,but another echinoderm,starfish,whose eggs are much bigger and transparent,has facilitated experimental approaches using microinjection and fluorescent imaging methodologies.Thus in starfish,it has been shown that the sperm-induced Ca2+ increase in the fertilized egg can be recapitulated by several Ca2+ -evoking second messengers,namely inositol 1,4,5-trisphosphate(InsP3) ,cyclic ADP-ribose(cADPr) and nicotinic acid adenine dinucleotide phosphate(NAADP) ,which may play distinct roles in the generation and propagation of the Ca2+ waves.Interestingly,it has also been found that the dynamic rearrangement of the actin cytoskeleton in the fertilized eggs plays pivotal roles in guiding monospermic sperm entry and in the fine modulation of the intracellular Ca2+ signaling.As it is well known that Ca2+ regulates the structure of the actin cytoskeleton,our finding that Ca2+ signaling can be reciprocally affected by the state of the actin cytoskeleton raises an intriguing possibility that actin and Ca2+ signaling may form a'positive feedback loop'that accelerates the downstream events of fertilization.Perturbation of the cortical actin networks also inhibits cortical granules exocytosis.Polymerizing actin bundles also compose the'acrosome process,'a tubular structure protruding from the head of fertilizing sperm. Hence,actin,which is one of the most strictly conserved proteins in e
