Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological cond...Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.展开更多
Astrocytes are not only the most populous cell type in the human brain,but they also have the most extensive and dive rse sets of connections,across synapses,axons,blood vessels,as well as having their own internal ne...Astrocytes are not only the most populous cell type in the human brain,but they also have the most extensive and dive rse sets of connections,across synapses,axons,blood vessels,as well as having their own internal network.Unsurprisingly,they are associated with many brain functions;from the synaptic transmission to energy metabolism and fluid homeostasis,and from cerebral blood flow and blood-brain barrier maintenance to neuroprotection,memory,immune defenses and detoxification,slee p,and early development.And yet,notwithstanding these key roles,so many current therapeutic approaches to a range of brain disorders have largely neglected their potential involvement.In this review,we consider the role of astrocytes in three brain therapies;two are emerging treatments(photobiomodulation and ultrasound),while the other is well-established(deep brain stimulation).In essence,we explore the issue of whether external sources,such as light,sound,or electricity,can influence the function of astrocytes,as they do neurons.We find that,when taken all together,each of these external sources can influence many,if not,all of the functions associated with astrocytes.These include influencing neuronal activity,prompting neuroprotection,reducing inflammation(astrogliosis) and potentially increasing cerebral blood flow and stimulating the glymphatic system.We suggest that astrocytes,just like neurons,can respond positively to each of these external applications and that their activation co uld each impart many beneficial outcomes on brain function;they are likely to be key playe rs underpinning the mechanisms behind many therapeutic strategies.展开更多
基金supported by Fonds Clinatec and COVEA France(to JM).
文摘Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.
基金Fonds de dotation Clinatec and COVEA France (to JM)。
文摘Astrocytes are not only the most populous cell type in the human brain,but they also have the most extensive and dive rse sets of connections,across synapses,axons,blood vessels,as well as having their own internal network.Unsurprisingly,they are associated with many brain functions;from the synaptic transmission to energy metabolism and fluid homeostasis,and from cerebral blood flow and blood-brain barrier maintenance to neuroprotection,memory,immune defenses and detoxification,slee p,and early development.And yet,notwithstanding these key roles,so many current therapeutic approaches to a range of brain disorders have largely neglected their potential involvement.In this review,we consider the role of astrocytes in three brain therapies;two are emerging treatments(photobiomodulation and ultrasound),while the other is well-established(deep brain stimulation).In essence,we explore the issue of whether external sources,such as light,sound,or electricity,can influence the function of astrocytes,as they do neurons.We find that,when taken all together,each of these external sources can influence many,if not,all of the functions associated with astrocytes.These include influencing neuronal activity,prompting neuroprotection,reducing inflammation(astrogliosis) and potentially increasing cerebral blood flow and stimulating the glymphatic system.We suggest that astrocytes,just like neurons,can respond positively to each of these external applications and that their activation co uld each impart many beneficial outcomes on brain function;they are likely to be key playe rs underpinning the mechanisms behind many therapeutic strategies.