Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is ...Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
MicroRNA-126 was involved in angiogenesis during physiological and pathological process. It was mainly expressed in endothelial cells, and defined as a pivotal biological molecule associated with vascular disease. Inc...MicroRNA-126 was involved in angiogenesis during physiological and pathological process. It was mainly expressed in endothelial cells, and defined as a pivotal biological molecule associated with vascular disease. Increased microRNA-126 in endothelial cells promotes angiogenesis in ischemic stroke, repairs impaired endothelial cells in atherosclerosis, and attenuates vascular dysfunction in diabetics. By contrast, microRNA-126 transferred from endothelial cell to smooth muscle cells could lead to proliferation that induced intimal hyperplasia. Additionally, microRNA-126 could be a tumor suppressor or an oncogene, which was depended on the cancer type. In this review, we summarized the function of microRNA-126 in ischemic stroke, atherosclerosis, diabetics, tumor, and discussed the underlying mechanisms.展开更多
基金supported by the National Key R&D Program of China,No.2019YFA0112000(to YHT)the National Natural Science Foundation of China,Nos.82071284(to YHT),81974179(to ZJZ)+4 种基金Shanghai Rising-Star Program,No.21QA1405200(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)the Notional Research Foundation of Korea,Nos.2020M3E5D9079912(to WSC),2021R1A2C3005704(to WSC),2022M3E5E8081188(to WSC)the Korea Health Technology R&D Project,No.HU20C0290(to WSC)。
文摘Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
基金This study was supported by grants from the National Key Research and Development Program of China(2016YFC1300600)the National Natural Science Foundation of China(81471178,GYY,81522015,YTW,81771251,GYY,81771244,ZJZ)+1 种基金K.C.Wong Education Foundationthe Science and Technology Commission of Shanghai Municipality(17ZR1413600,ZJZ).
文摘MicroRNA-126 was involved in angiogenesis during physiological and pathological process. It was mainly expressed in endothelial cells, and defined as a pivotal biological molecule associated with vascular disease. Increased microRNA-126 in endothelial cells promotes angiogenesis in ischemic stroke, repairs impaired endothelial cells in atherosclerosis, and attenuates vascular dysfunction in diabetics. By contrast, microRNA-126 transferred from endothelial cell to smooth muscle cells could lead to proliferation that induced intimal hyperplasia. Additionally, microRNA-126 could be a tumor suppressor or an oncogene, which was depended on the cancer type. In this review, we summarized the function of microRNA-126 in ischemic stroke, atherosclerosis, diabetics, tumor, and discussed the underlying mechanisms.