Objective To evaluate the influence of hypothermia to Ca 2+/calmodulin-dependent kinase Ⅱ during global brain ischemia in rats. Methods Fifteen male SD rats were randomly divided into 3 groups: control group (group ...Objective To evaluate the influence of hypothermia to Ca 2+/calmodulin-dependent kinase Ⅱ during global brain ischemia in rats. Methods Fifteen male SD rats were randomly divided into 3 groups: control group (group Ⅰ, n=5), hepothermia group (group Ⅱ, n=5) and reperfusion group (group Ⅲ, n=5). Only sugery was performed without hypothermia and clipping bilateral carotids in group Ⅰ. Ice was used covering head of rats in group Ⅱ to get hypothermia around 32℃, and bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion keeping tympanum temperature 32℃. Bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion without hypothermia in Group Ⅲ. Brain tissues were saved in three groups after experiments for evaluating Ca 2+/calmodulin-dependent kinase Ⅱ. Results Left tympanum temperature in the group Ⅱ is significantly lower than group Ⅰ during global ischemia and reperfusion(p<0.05). Those are no difference between group Ⅰ and group Ⅲ. The activity of Ca 2+/calmodulin-dependent kinase Ⅱ after 60 min reperfusion in both Group Ⅱ and group Ⅲ was significantly lower than those in the group Ⅰ(P<0.05), which is significantly higher in the group Ⅱ than in the group Ⅲ(P<0.05). Conclusion Hypothermia can increase the activity of Ca 2+/calmodulin-dependent kinase Ⅱ after global ischemia reperfusion. Hypothermia has significant protection during ischemia reperfusion injury.展开更多
BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, M...BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, MTT assay and hoechst dye staining to check this mechanism in SKNSH and U251 cell lines. [WT5”BX]Results. Both 2mmol/L H 2O 2 and 0 5 μ mol/L amyloid β protein (Aβ) induce these two cell lines die via apoptosis. Either melatonin or glutathione can significantly protect both cell lines. The protective effect of 10 μ mol/L melatonin is as same as that of 60 μ mol/L glutathione. [WT5”BX]Conclusion. Melatonin can partly inhibit the cytotoxicity of H 2O 2 and Aβ through its role as a free radical scavenger.展开更多
Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that in...Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell （RGC） survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microgUal activation, partly via the action of stanniocalcin 1 （STCl）. Furthermore, we found that microRNA-21a-Sp （miR-21） and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/ PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR- 21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.展开更多
OBJECTIVE:To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and invitromodels of cerebral ischemia.METHODS:As an in vitro model,oxygen glucose deprivation followed by reoxygenat...OBJECTIVE:To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and invitromodels of cerebral ischemia.METHODS:As an in vitro model,oxygen glucose deprivation followed by reoxygenation(OGD-R)and hydrogen peroxide(H2O2)induced cellular damage in rat pheochromocytoma(PC12)cells was used to investigate the neuroprotective effects of extract of Fructus Chebulae.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to calculate cell survival.For in vivo,occlusion of left middle cerebral artery on rats was carried out as a focal cerebral ischemic model.RESULTS:Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2by 68%and 91.4%respectively.Fructus Chebulae also de-creases the cerebral infarct volume by 39%and extent of hemisphere swelling from 17%in control group to 10%in FructusChebulaetreated group.CONCLUSION:Fructus Chebulae,as a traditional medicine,can rescue the neuronal cell death against ischemia related damage.The possible mechanism for the neuroprotection might be the inhibition of oxidative damages occurring after acute phase of cerebral ischemia.展开更多
Objective: To investigate the effect of liposome-mediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats. Methods: Sixt...Objective: To investigate the effect of liposome-mediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats. Methods: Sixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RT-PCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale. Results: RT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1 week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group ((20.4)±(3.2), (21.7)±(3.6), (22.5)±(3.4)) was more than that in control group ((16.8)±(2.8), (17.3)±(2.7), (18.2)±(3.2), P<(0.05)). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group ((74.2)±(25.8), (98.7)±(31.6)) was less than that in control group ((98.5)±(32.2), (134.6)±(45.2), P<(0.01)), and the mean gray of ACP in GDNF group ((84.5)±(32.6), (79.5)±(28.4)) was more than that in control group ((61.2)±(24.9), (52.6)±(19.9), P<(0.01)). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<(0.05)). Conclusions: GDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incompleted spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating traumatic spinal cord injury.展开更多
文摘Objective To evaluate the influence of hypothermia to Ca 2+/calmodulin-dependent kinase Ⅱ during global brain ischemia in rats. Methods Fifteen male SD rats were randomly divided into 3 groups: control group (group Ⅰ, n=5), hepothermia group (group Ⅱ, n=5) and reperfusion group (group Ⅲ, n=5). Only sugery was performed without hypothermia and clipping bilateral carotids in group Ⅰ. Ice was used covering head of rats in group Ⅱ to get hypothermia around 32℃, and bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion keeping tympanum temperature 32℃. Bilateral carotids were clipped 20 min of ischemia followed by 60 min reperfusion without hypothermia in Group Ⅲ. Brain tissues were saved in three groups after experiments for evaluating Ca 2+/calmodulin-dependent kinase Ⅱ. Results Left tympanum temperature in the group Ⅱ is significantly lower than group Ⅰ during global ischemia and reperfusion(p<0.05). Those are no difference between group Ⅰ and group Ⅲ. The activity of Ca 2+/calmodulin-dependent kinase Ⅱ after 60 min reperfusion in both Group Ⅱ and group Ⅲ was significantly lower than those in the group Ⅰ(P<0.05), which is significantly higher in the group Ⅱ than in the group Ⅲ(P<0.05). Conclusion Hypothermia can increase the activity of Ca 2+/calmodulin-dependent kinase Ⅱ after global ischemia reperfusion. Hypothermia has significant protection during ischemia reperfusion injury.
基金This project is supported by Korea Science & EngineeringFoundation (KOSEF) and Korea Ministry of Science &Technology
文摘BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, MTT assay and hoechst dye staining to check this mechanism in SKNSH and U251 cell lines. [WT5”BX]Results. Both 2mmol/L H 2O 2 and 0 5 μ mol/L amyloid β protein (Aβ) induce these two cell lines die via apoptosis. Either melatonin or glutathione can significantly protect both cell lines. The protective effect of 10 μ mol/L melatonin is as same as that of 60 μ mol/L glutathione. [WT5”BX]Conclusion. Melatonin can partly inhibit the cytotoxicity of H 2O 2 and Aβ through its role as a free radical scavenger.
基金This study was partially supported by the Natural Science Foundation of China （81470627 and 81670897）, key projects from the Natural Science Foundation of Guangdong Province （201_4A030308005）, and Guangdong Natural Science Funds for Distinguished Young Scholar （2016A030306006）.
文摘Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell （RGC） survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microgUal activation, partly via the action of stanniocalcin 1 （STCl）. Furthermore, we found that microRNA-21a-Sp （miR-21） and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/ PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR- 21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.
基金Supported by a Grant of the Korean Health Technology Re-search and Development Project,Ministry of Health&Wel-fare(B110072)National Research Foundation of Korea Funded by the Ministry of Science,Information and Commu-nication Technology&Future Planning,Republic of Korea(2012M3A9C4048795)
文摘OBJECTIVE:To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and invitromodels of cerebral ischemia.METHODS:As an in vitro model,oxygen glucose deprivation followed by reoxygenation(OGD-R)and hydrogen peroxide(H2O2)induced cellular damage in rat pheochromocytoma(PC12)cells was used to investigate the neuroprotective effects of extract of Fructus Chebulae.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to calculate cell survival.For in vivo,occlusion of left middle cerebral artery on rats was carried out as a focal cerebral ischemic model.RESULTS:Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2by 68%and 91.4%respectively.Fructus Chebulae also de-creases the cerebral infarct volume by 39%and extent of hemisphere swelling from 17%in control group to 10%in FructusChebulaetreated group.CONCLUSION:Fructus Chebulae,as a traditional medicine,can rescue the neuronal cell death against ischemia related damage.The possible mechanism for the neuroprotection might be the inhibition of oxidative damages occurring after acute phase of cerebral ischemia.
文摘Objective: To investigate the effect of liposome-mediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats. Methods: Sixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RT-PCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale. Results: RT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1 week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group ((20.4)±(3.2), (21.7)±(3.6), (22.5)±(3.4)) was more than that in control group ((16.8)±(2.8), (17.3)±(2.7), (18.2)±(3.2), P<(0.05)). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group ((74.2)±(25.8), (98.7)±(31.6)) was less than that in control group ((98.5)±(32.2), (134.6)±(45.2), P<(0.01)), and the mean gray of ACP in GDNF group ((84.5)±(32.6), (79.5)±(28.4)) was more than that in control group ((61.2)±(24.9), (52.6)±(19.9), P<(0.01)). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<(0.05)). Conclusions: GDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incompleted spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating traumatic spinal cord injury.
