We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Ch...BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Chinese medicinal substances may play an important role in the expression of Syp and PSD-95. OBJECTIVE： To observe the effect of Panaxtriol Saponins （PTS）, an active component in Sanqi tongshu capsules, on the expression of Syp and PSD-95 after cerebral infarction at different time points in rats, so as to examine the cerebral function remodeling mechanism. DESIGN, TIME AND SETTING： A randomized and controlled observation which was performed in Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine from January to March, 2007. MATERIALS： Twenty-six healthy male Sprague Dawley rats were used to establish middle cerebral artery occlusion based on the Longa method. Sanqi tongshu capsules （containing 100 mg PTS per tablet） were provided by the Chengdu Huashen Group and nimodipine tablets （30 mg） by Tianjin Zhongyang Pharmaceutical Co., Ltd. METHODS： Twenty-six rats were randomly divided into an operation group （n = 21 ） and a control group （n = 5）. The operation group underwent the EZ Longa procedure to make the middle cerebral artery occlusion model. After surgery rats were randomly divided into a model group, a PTS group and a nimodipine group, with seven rats in each group. Rats were intragastrically administrated with saline （2 mL/d） in the model group, with Sanqi tongshu capsule （5.4 mg/100 g/d） in the PTS group, and with nimodipine （1.73 mg/100 g/d） in the nimodipine group. Rats in the control group did not undergo model establishment and drug administration. MAIN OUTCOME MEASURES： The expressions of Syp and PSD-95 were measured by immunohistochemical and image analysis at days 3, 7 and 28 after the operation. RESULTS： The expression of Syp and PSD-95 in the operation group was significantly lower than in the control group at days 3, 7, 28 postoperatively （P 〈 0.05）. The expression of Syp and PSD-95 in the PTS group and nimodipine group was significantly higher than in the model group at day 28 postoperatively （P 〈 0.05-0.01）. Additionally, after PTS and nimodipine treatment at different intervals, the expression of Syp and PSD-95 at day 28 postoperatively was significantly higher than those at days 3 and 7 postoperatively, respectively （P 〈 0.01）. CONCLUSION： PTS can promote the expression of Syp and PSD-95, i.e. the remodeling process of synapses, after cerebral infarction at different time points in rats, which contributes to cerebral function remodeling.展开更多
It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in...It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in ische-mic area reacting to ischemia after transient middle cerebral artery occlusion ( MCAO) by Western immunoblot analy-展开更多
Objective： To investigate the effects of sodium ferulate （SF）, an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 （PSD-95） and neuroprotection after transient cerebr...Objective： To investigate the effects of sodium ferulate （SF）, an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 （PSD-95） and neuroprotection after transient cerebral artery occlusion in rats. Methods： Forty-six male Sprague-Dawley rats were randomized into 2 groups （ n = 23 in each group） ： the control group and the SF group. After anesthesia, the middle cerebral artery occlusion （MCAO） was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.^ 8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 （ PSD- 95 ） was studied with Western blot analysis system in the cortex and striatum of rat brain. Results ： The neurologic deficit score of the SF group decreased substantially compared with that of the control group （ P 〈0.05）. The infarct volume of the control group （168.1 mm^3 ± 42.2 mm^3） was significantly larger than that of the SF group （61.5 mm^3 ± 28.7 mm^3 ） at 24 hours after reperfusion （P 〈 0.01 ）. And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex. Conclusions ： Sodium ferulate can induce a neuroproteetive effect against the transient focal cerebral isehemie injury and weaken the activation of PSD-95 in isehemie area after MCAO.展开更多
Dendrobium nobile Lindl.alkaloids（DNLA）,the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons ag...Dendrobium nobile Lindl.alkaloids（DNLA）,the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose deprivation.However,it is not clear whether DNLA reduces amyloid-beta（Aβ）-induced neuronal injury.In this study,cortical neurons were treated with DNLA at different concentrations（0.025,0.25,and 2.5 mg/L）for 24 hours,followed by administration of Aβ（25-35）（10μM）.Aβ（25-35） treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial tumefaction.The damage caused by Aβ（25-35） on these cellular properties was markedly attenuated when cells were pretreated with DNLA.Treatment with Aβ（25-35）down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with DNLA.These findings suggest that DNLA reduces the cytotoxicity induced by Aβ（25-35） in rat primary cultured neurons.The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.
基金the National Natural Science Foundation of China,No.30472214
文摘BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Chinese medicinal substances may play an important role in the expression of Syp and PSD-95. OBJECTIVE： To observe the effect of Panaxtriol Saponins （PTS）, an active component in Sanqi tongshu capsules, on the expression of Syp and PSD-95 after cerebral infarction at different time points in rats, so as to examine the cerebral function remodeling mechanism. DESIGN, TIME AND SETTING： A randomized and controlled observation which was performed in Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine from January to March, 2007. MATERIALS： Twenty-six healthy male Sprague Dawley rats were used to establish middle cerebral artery occlusion based on the Longa method. Sanqi tongshu capsules （containing 100 mg PTS per tablet） were provided by the Chengdu Huashen Group and nimodipine tablets （30 mg） by Tianjin Zhongyang Pharmaceutical Co., Ltd. METHODS： Twenty-six rats were randomly divided into an operation group （n = 21 ） and a control group （n = 5）. The operation group underwent the EZ Longa procedure to make the middle cerebral artery occlusion model. After surgery rats were randomly divided into a model group, a PTS group and a nimodipine group, with seven rats in each group. Rats were intragastrically administrated with saline （2 mL/d） in the model group, with Sanqi tongshu capsule （5.4 mg/100 g/d） in the PTS group, and with nimodipine （1.73 mg/100 g/d） in the nimodipine group. Rats in the control group did not undergo model establishment and drug administration. MAIN OUTCOME MEASURES： The expressions of Syp and PSD-95 were measured by immunohistochemical and image analysis at days 3, 7 and 28 after the operation. RESULTS： The expression of Syp and PSD-95 in the operation group was significantly lower than in the control group at days 3, 7, 28 postoperatively （P 〈 0.05）. The expression of Syp and PSD-95 in the PTS group and nimodipine group was significantly higher than in the model group at day 28 postoperatively （P 〈 0.05-0.01）. Additionally, after PTS and nimodipine treatment at different intervals, the expression of Syp and PSD-95 at day 28 postoperatively was significantly higher than those at days 3 and 7 postoperatively, respectively （P 〈 0.01）. CONCLUSION： PTS can promote the expression of Syp and PSD-95, i.e. the remodeling process of synapses, after cerebral infarction at different time points in rats, which contributes to cerebral function remodeling.
基金Supported by the"Tenth five-year-plan"Medical Science Foundation of PLA(No.01M118).
文摘It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in ische-mic area reacting to ischemia after transient middle cerebral artery occlusion ( MCAO) by Western immunoblot analy-
文摘Objective： To investigate the effects of sodium ferulate （SF）, an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 （PSD-95） and neuroprotection after transient cerebral artery occlusion in rats. Methods： Forty-six male Sprague-Dawley rats were randomized into 2 groups （ n = 23 in each group） ： the control group and the SF group. After anesthesia, the middle cerebral artery occlusion （MCAO） was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.^ 8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 （ PSD- 95 ） was studied with Western blot analysis system in the cortex and striatum of rat brain. Results ： The neurologic deficit score of the SF group decreased substantially compared with that of the control group （ P 〈0.05）. The infarct volume of the control group （168.1 mm^3 ± 42.2 mm^3） was significantly larger than that of the SF group （61.5 mm^3 ± 28.7 mm^3 ） at 24 hours after reperfusion （P 〈 0.01 ）. And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex. Conclusions ： Sodium ferulate can induce a neuroproteetive effect against the transient focal cerebral isehemie injury and weaken the activation of PSD-95 in isehemie area after MCAO.
基金financially supported by the National Natural Science Foundation of China,No.81473201the Natural Science Foundation of Educational Commission of Guizhou Province of China,No.2010043+1 种基金the Science and Technology Foundation of Guizhou Province of China,No.JZ[2014]2016the Modernization of Traditional Chinese Medicine Project of Guizhou Province of China,No.[2011]5086
文摘Dendrobium nobile Lindl.alkaloids（DNLA）,the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose deprivation.However,it is not clear whether DNLA reduces amyloid-beta（Aβ）-induced neuronal injury.In this study,cortical neurons were treated with DNLA at different concentrations（0.025,0.25,and 2.5 mg/L）for 24 hours,followed by administration of Aβ（25-35）（10μM）.Aβ（25-35） treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial tumefaction.The damage caused by Aβ（25-35） on these cellular properties was markedly attenuated when cells were pretreated with DNLA.Treatment with Aβ（25-35）down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with DNLA.These findings suggest that DNLA reduces the cytotoxicity induced by Aβ（25-35） in rat primary cultured neurons.The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.
