Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injur...Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.展开更多
Traumatic brain injury is an important global public health problem.Traumatic brain injury not only causes neural cell death,but also induces dendritic spine degeneration.Spared neurons from cell death in the injured ...Traumatic brain injury is an important global public health problem.Traumatic brain injury not only causes neural cell death,but also induces dendritic spine degeneration.Spared neurons from cell death in the injured brain may exhibit dendrite damage,dendritic spine degeneration,mature spine loss,synapse loss,and impairment of activity.Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury.Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells.During synaptic plasticity,the numbers and shapes of dendritic spines undergo dynamic reorganization.Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation,while spine shrinkage and retraction are associated with long-term depression.Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses.To date,there is no effective treatment to prevent dendritic degeneration and synapse loss.This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury.The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive,possibly including blocking activation of Cofilin induced by beta amyloid,Ras activation,and inhibition of GSK-3 signaling pathway.Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.展开更多
Traumatic brain injury（TBI） is one of the major causes of death and disability worldwide.No effective treatment has been identified from clinical trials.Compelling evidence exists that treatment with mesenchymal ste...Traumatic brain injury（TBI） is one of the major causes of death and disability worldwide.No effective treatment has been identified from clinical trials.Compelling evidence exists that treatment with mesenchymal stem cells（MSCs） exerts a substantial therapeutic effect after experimental brain injury.In addition to their soluble factors,therapeutic effects of MSCs may be attributed to their generation and release of exosomes.Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types.Exosomes play a pivotal role in intercellular communication.Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI.Therapeutic effects of exosomes derive from the exosome content,especially micro RNAs（mi RNAs）.mi RNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes.Compared with their parent cells,exosomes are more stable and can cross the blood-brain barrier.They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells.Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery,potentially for a variety of neural injuries and neurodegenerative diseases.This review discusses the most recent knowledge of exosome therapies for TBI,their associated challenges and opportunities.展开更多
Traumatic brain injury （TBI）： Despite improved supportive and rehabilitative care of TBI patients, TBI remains a leading cause of death and disability worldwide. To date, no effective pharmacological treatments are...Traumatic brain injury （TBI）： Despite improved supportive and rehabilitative care of TBI patients, TBI remains a leading cause of death and disability worldwide. To date, no effective pharmacological treatments are available for TBI. The mechanisms underlying brain damage and repair following TBI are complex and not completely understood. Coagulopathy after TBI is frequent and an independent prognostic factor for unfavorable outcome and prognosis （Stein and Smith, 2004）. It may be amenable to treatment, and effective management of coagulopathy may protect from secondary injury and poor outcomes. Although the main challenge for TBI management is to address the risk of hypocoagulopathy with prolonged bleeding and progression of hemorrhagic lesions, the risk of hypercoagulopathy with an increased microthrombosis formation warrants investigation to reduce neurological deficits after TBI.展开更多
Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease,...Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease, Parkinson＇s disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.展开更多
基金supported by Notional Institutes of Health Grant,No.1R01NS100710-01A1(to YX)。
文摘Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.
文摘Traumatic brain injury is an important global public health problem.Traumatic brain injury not only causes neural cell death,but also induces dendritic spine degeneration.Spared neurons from cell death in the injured brain may exhibit dendrite damage,dendritic spine degeneration,mature spine loss,synapse loss,and impairment of activity.Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury.Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells.During synaptic plasticity,the numbers and shapes of dendritic spines undergo dynamic reorganization.Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation,while spine shrinkage and retraction are associated with long-term depression.Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses.To date,there is no effective treatment to prevent dendritic degeneration and synapse loss.This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury.The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive,possibly including blocking activation of Cofilin induced by beta amyloid,Ras activation,and inhibition of GSK-3 signaling pathway.Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.
基金supported by National Institute of Neurological Disorders and Stroke(NINDS)of the National Institutes of Health under award number R01 NS088656 to MC
文摘Traumatic brain injury（TBI） is one of the major causes of death and disability worldwide.No effective treatment has been identified from clinical trials.Compelling evidence exists that treatment with mesenchymal stem cells（MSCs） exerts a substantial therapeutic effect after experimental brain injury.In addition to their soluble factors,therapeutic effects of MSCs may be attributed to their generation and release of exosomes.Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types.Exosomes play a pivotal role in intercellular communication.Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI.Therapeutic effects of exosomes derive from the exosome content,especially micro RNAs（mi RNAs）.mi RNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes.Compared with their parent cells,exosomes are more stable and can cross the blood-brain barrier.They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells.Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery,potentially for a variety of neural injuries and neurodegenerative diseases.This review discusses the most recent knowledge of exosome therapies for TBI,their associated challenges and opportunities.
文摘Traumatic brain injury （TBI）： Despite improved supportive and rehabilitative care of TBI patients, TBI remains a leading cause of death and disability worldwide. To date, no effective pharmacological treatments are available for TBI. The mechanisms underlying brain damage and repair following TBI are complex and not completely understood. Coagulopathy after TBI is frequent and an independent prognostic factor for unfavorable outcome and prognosis （Stein and Smith, 2004）. It may be amenable to treatment, and effective management of coagulopathy may protect from secondary injury and poor outcomes. Although the main challenge for TBI management is to address the risk of hypocoagulopathy with prolonged bleeding and progression of hemorrhagic lesions, the risk of hypercoagulopathy with an increased microthrombosis formation warrants investigation to reduce neurological deficits after TBI.
文摘Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease, Parkinson＇s disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.
