Neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease and amyotrophic lateral sclerosis,are a group of incurable neurological disorders,characterized by the chronic progr...Neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease and amyotrophic lateral sclerosis,are a group of incurable neurological disorders,characterized by the chronic progressive loss of different neuronal subtypes.However,despite its increasing prevalence among the everincreasing aging population,little progress has been made in the coincident immense efforts towards development of therapeutic agents.Research interest has recently turned towards stem cells including stem cells-derived exosomes,neurotrophic factors,and their combination as potential therapeutic agents in neurodegenerative diseases.In this review,we summarize the progress in therapeutic strategies based on stem cells combined with neurotrophic factors and mesenchymal stem cells-derived exosomes for neurodegenerative diseases,with an emphasis on the combination therapy.展开更多
Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,however no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with ...Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,however no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with white matter damage,we found that this damage is associated with disorganized cortical structure.In a mouse model,optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell(OPC)proliferation,remyelination in the corpus callosum,and recovery of cognitive ability after cerebral hypoperfusion.The therapeutic effect of such stimulation was restricted to the upper layers of the cortex,but also spanned a wide time window after ischemia.Mechanistically,enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons.Additionally,skin stroking,an easier method to translate into clinical practice,activated the somatosensory cortex,thereby promoting OPC proliferation,remyelination and cognitive recovery following cerebral hypoperfusion.In summary,we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion.It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.展开更多
Dear Editor,Neuropathic pain(NeuP)is known as a common and notorious neurological disease,characterized by spontaneous pain and evoked abnormal pain that includes hypersensitivity to external innocuous(allodynia)and n...Dear Editor,Neuropathic pain(NeuP)is known as a common and notorious neurological disease,characterized by spontaneous pain and evoked abnormal pain that includes hypersensitivity to external innocuous(allodynia)and noxious stimulation(hyperalgesia).Allodynia is especially torturous because gentle touch may trigger pain.展开更多
Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological st...Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures（FSs） in infancy. Here we used a well-established complex FS model in rats and showed that：（1） the susceptibility to seizures induced by hyperthermia, pentylenetetrazol（PTZ）, and maximal electroshock（MES） was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats;（2） adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and（3） the protein expression of interleukin-1β, an infl ammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.展开更多
In the original publication of the article, the representativeEEG of female rat pups with FS in Figure 1 C and D wasincorrectly intercepted from that of male rat pups. Thiscorrection does not affect the conclusions of...In the original publication of the article, the representativeEEG of female rat pups with FS in Figure 1 C and D wasincorrectly intercepted from that of male rat pups. Thiscorrection does not affect the conclusions of the paper.Figure 1 has been corrected on the online PDF version anddisplayed below.展开更多
基金Supported by the Social Development Project of Jiangsu Science and Technology Department,No.BE2015721。
文摘Neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease and amyotrophic lateral sclerosis,are a group of incurable neurological disorders,characterized by the chronic progressive loss of different neuronal subtypes.However,despite its increasing prevalence among the everincreasing aging population,little progress has been made in the coincident immense efforts towards development of therapeutic agents.Research interest has recently turned towards stem cells including stem cells-derived exosomes,neurotrophic factors,and their combination as potential therapeutic agents in neurodegenerative diseases.In this review,we summarize the progress in therapeutic strategies based on stem cells combined with neurotrophic factors and mesenchymal stem cells-derived exosomes for neurodegenerative diseases,with an emphasis on the combination therapy.
基金We would like to thank the Core Facilities,Zhejiang University School of Medicine for technical support.This work was supported by the National Natural Science Foundation of China(81973302,81903580)the National Key R&D Program of China(2020YFA0803900)the Zhejiang Provincial Natural Science Foundation of China(LR17H310001,LYY22H310003).
文摘Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,however no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with white matter damage,we found that this damage is associated with disorganized cortical structure.In a mouse model,optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell(OPC)proliferation,remyelination in the corpus callosum,and recovery of cognitive ability after cerebral hypoperfusion.The therapeutic effect of such stimulation was restricted to the upper layers of the cortex,but also spanned a wide time window after ischemia.Mechanistically,enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons.Additionally,skin stroking,an easier method to translate into clinical practice,activated the somatosensory cortex,thereby promoting OPC proliferation,remyelination and cognitive recovery following cerebral hypoperfusion.In summary,we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion.It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.
基金This work was supported by grants from National Natural Science Foundation of China(81872843,81673404,and 81821091).
文摘Dear Editor,Neuropathic pain(NeuP)is known as a common and notorious neurological disease,characterized by spontaneous pain and evoked abnormal pain that includes hypersensitivity to external innocuous(allodynia)and noxious stimulation(hyperalgesia).Allodynia is especially torturous because gentle touch may trigger pain.
基金supported by the National Natural Science Foundation of China (91332202,81201007,and 81302749)the Doctoral Fund of the Ministry of Education of China (20120101120070)the China Postdoctoral Science Foundation (2013M531476)
文摘Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures（FSs） in infancy. Here we used a well-established complex FS model in rats and showed that：（1） the susceptibility to seizures induced by hyperthermia, pentylenetetrazol（PTZ）, and maximal electroshock（MES） was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats;（2） adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and（3） the protein expression of interleukin-1β, an infl ammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.
文摘In the original publication of the article, the representativeEEG of female rat pups with FS in Figure 1 C and D wasincorrectly intercepted from that of male rat pups. Thiscorrection does not affect the conclusions of the paper.Figure 1 has been corrected on the online PDF version anddisplayed below.
