Objective This review discusses the current status and progress in studies on the roles of hydrogen sulfide （H2S） in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic poten...Objective This review discusses the current status and progress in studies on the roles of hydrogen sulfide （H2S） in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders. Data sources The data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011. The search terms were ＂hydrogen sulfide＂, ＂neuron＂, and ＂neurodegenerative disorders＂. Study selection Articles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H2S were selected. Results The inhibited generation of endogenous H2S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H2S elicits neuroprotection in Alzheimer＇s disease and Parkinson＇s disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H2S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator CI channels. H2S regulates the long-term potentiation （LTP） and GABAB receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and gila cells. Conclusions These articles suggest that endogenous H2S may regulate the toxicity of neurotoxin. H2S not only acts as a neuroprotectant but also serves as a novel neuromodulator.展开更多
Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain.Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the b...Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain.Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain,where the ischemic cascade eventually leads to cell death and brain infarction.Extensive researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic stroke.However,traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment efficacy.Nanomedicine provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo,achieve effective drug accumulation at the target site,enhance the therapeutic effect and meanwhile reduce the side effect.In this review,we comprehensively describe the pathophysiology of stroke,traditional treatment strategies and emerging nanomedicines,summarize the barriers and methods for transporting nanomedicine to the lesions,and illustrate the latest progress of nanomedicine in treating ischemic stroke,with a view to providing a new feasible path for the treatment of cerebral ischemia.展开更多
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Adjunctive melatonin use in schizophrenia, as supported by a modicum ofevidence, has multiple transcending chronobiotic actions, including fixingconcurrent sleep problems to bona fide augmentative antipsychotic action...Adjunctive melatonin use in schizophrenia, as supported by a modicum ofevidence, has multiple transcending chronobiotic actions, including fixingconcurrent sleep problems to bona fide augmentative antipsychotic actions,mitigating the risk of tardive dyskinesias, curbing the drastic metabolic syndromeand ultimately providing neuroprotective actions. Its use is rather an art thanscience!展开更多
基金The study was supported by the grants from the Natural Science Foundation of China （No. 81071005 and No. 30770740） and from the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry （No.[2010]508）.
文摘Objective This review discusses the current status and progress in studies on the roles of hydrogen sulfide （H2S） in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders. Data sources The data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011. The search terms were ＂hydrogen sulfide＂, ＂neuron＂, and ＂neurodegenerative disorders＂. Study selection Articles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H2S were selected. Results The inhibited generation of endogenous H2S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H2S elicits neuroprotection in Alzheimer＇s disease and Parkinson＇s disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H2S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator CI channels. H2S regulates the long-term potentiation （LTP） and GABAB receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and gila cells. Conclusions These articles suggest that endogenous H2S may regulate the toxicity of neurotoxin. H2S not only acts as a neuroprotectant but also serves as a novel neuromodulator.
基金the support from the International Cooperative project of the National Key R&D Program of China(Grant No.2017YFE0126900)National Natural Science Foundation of China(Grant No.81872808)+2 种基金Program of Shanghai Academic Research Leader(18XD1400500,China)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,China)ZJ Lab
文摘Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain.Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain,where the ischemic cascade eventually leads to cell death and brain infarction.Extensive researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic stroke.However,traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment efficacy.Nanomedicine provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo,achieve effective drug accumulation at the target site,enhance the therapeutic effect and meanwhile reduce the side effect.In this review,we comprehensively describe the pathophysiology of stroke,traditional treatment strategies and emerging nanomedicines,summarize the barriers and methods for transporting nanomedicine to the lesions,and illustrate the latest progress of nanomedicine in treating ischemic stroke,with a view to providing a new feasible path for the treatment of cerebral ischemia.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
文摘Adjunctive melatonin use in schizophrenia, as supported by a modicum ofevidence, has multiple transcending chronobiotic actions, including fixingconcurrent sleep problems to bona fide augmentative antipsychotic actions,mitigating the risk of tardive dyskinesias, curbing the drastic metabolic syndromeand ultimately providing neuroprotective actions. Its use is rather an art thanscience!
