Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is ne...Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.展开更多
Cascading reactions in fluorophores accompanied by the replacement of different fluorescence wavelengths can be used to develop luminescent materials and reactive fluorescent probes.Based on multiple signal channels,t...Cascading reactions in fluorophores accompanied by the replacement of different fluorescence wavelengths can be used to develop luminescent materials and reactive fluorescent probes.Based on multiple signal channels,the selectivity of probes can be improved and the range of response to guest molecule recognition can be expanded.By regulating the position,number,and activity of active sites in fluorophores,fluorescent probes that successively react with thiol and amino groups in cysteine(Cys),homocysteine(Hcy)have been developed,which can only react with the thiol group of GSH,In this paper,we report the first probe capable of cascading nucleophilic substitution reaction with the thiol group and amino group of GSH at a single reaction site,and showed the dual-color recognition of GSH,which improved the selectivity of GSH also was an extension of GSH probes.The probe Rho-DEA was based on a TICS fluorophore,and the intramolecular cascade nucleophilic substitution reaction occurs with Cys/Hcy.The thiol substitution of the first step reaction with Cys/Hcy was quenched due to intersystem crossing to triplet state,so GSH can be selectively recognized from the fluorescence signal.Rho-DEA has the ability of mitochondrial localization,and finally realized in situ dual-color fluorescence recognition of GSH in mitochondria.展开更多
基金supported by a grant from the Guangdong Science&Technology Plan Program in China,No.2014A020212043the a grant from the Shenzhen Science&Technology Plan Program in China,No.JCYJ20140414170821242+1 种基金the a grant from Shenzhen Collaborative Innovation Plan Program in China,No.GJHZ20120614154914623a grant from the Science&Technology Project of Shanxi Health and Family Planning Commission in China,No.201201060
文摘Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia（at 33°C）, or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.
基金supported by the National Natural Science Foundation of China(Nos.22078314,21878286,21908216)。
文摘Cascading reactions in fluorophores accompanied by the replacement of different fluorescence wavelengths can be used to develop luminescent materials and reactive fluorescent probes.Based on multiple signal channels,the selectivity of probes can be improved and the range of response to guest molecule recognition can be expanded.By regulating the position,number,and activity of active sites in fluorophores,fluorescent probes that successively react with thiol and amino groups in cysteine(Cys),homocysteine(Hcy)have been developed,which can only react with the thiol group of GSH,In this paper,we report the first probe capable of cascading nucleophilic substitution reaction with the thiol group and amino group of GSH at a single reaction site,and showed the dual-color recognition of GSH,which improved the selectivity of GSH also was an extension of GSH probes.The probe Rho-DEA was based on a TICS fluorophore,and the intramolecular cascade nucleophilic substitution reaction occurs with Cys/Hcy.The thiol substitution of the first step reaction with Cys/Hcy was quenched due to intersystem crossing to triplet state,so GSH can be selectively recognized from the fluorescence signal.Rho-DEA has the ability of mitochondrial localization,and finally realized in situ dual-color fluorescence recognition of GSH in mitochondria.
