Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic reso...Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic resonance imaging(MRI) scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke.This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models.It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke.The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke.Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke.Administration in vivo of miR-130 a inhibitor or miRNA mimic(miR-367,miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes.展开更多
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested c...Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.展开更多
Experimental stroke research commonly employs focal cerebral ischemic rat models (Bederson et al., 1986a; Longa et al., 1989). In human patients, ischemic stroke typically results from thrombotic or embolic occlusio...Experimental stroke research commonly employs focal cerebral ischemic rat models (Bederson et al., 1986a; Longa et al., 1989). In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery (MCA). Experimental focal cerebral ischemia models have been employed to mimic human stroke (Durukan and Tatlisumak, 2007). Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA (MCA occlusion, MCAO) (Rosamond et al., 2008). Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms (Liu and McCullough, 2011). Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions (Armstead et al., 2010). During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.展开更多
The optimal protocol for neuromodulation by transcranial direct current stimulation(tDCS)remains unclear.Using the rotarod paradigm,we found that mouse motor learning was enhanced by anodal tDCS(3.2 mA/cm^(2))during b...The optimal protocol for neuromodulation by transcranial direct current stimulation(tDCS)remains unclear.Using the rotarod paradigm,we found that mouse motor learning was enhanced by anodal tDCS(3.2 mA/cm^(2))during but not before or after the performance of a task.Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS.Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner.Transcranial in vivo Ca^(2+)imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex(M1).Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance,suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement.Thus,application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.展开更多
文摘Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic resonance imaging(MRI) scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke.This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models.It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke.The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke.Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke.Administration in vivo of miR-130 a inhibitor or miRNA mimic(miR-367,miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes.
基金supported by the National Natural Science Foundation of China,No.81000852 and 81301677the AHA Award,No.17POST32530004+1 种基金the Supporting Project of Science & Technology of Sichuan Province of China,No.2012SZ0140the Research Foundation of Zhejiang Province of China,No.201022896
文摘Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.
基金supported by the 2013 Inje University Research Grant
文摘Experimental stroke research commonly employs focal cerebral ischemic rat models (Bederson et al., 1986a; Longa et al., 1989). In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery (MCA). Experimental focal cerebral ischemia models have been employed to mimic human stroke (Durukan and Tatlisumak, 2007). Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA (MCA occlusion, MCAO) (Rosamond et al., 2008). Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms (Liu and McCullough, 2011). Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions (Armstead et al., 2010). During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32070100)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)+2 种基金the Shanghai Key Basic Research Project(18JC1410100)Lingang Lab(LG202106-04-03 and LG202105-01-07)the Shanghai Pilot Program for Basic Research–Chinese Academy of Science,Shanghai Branch(JCYJ-SHFY-2022-010).
文摘The optimal protocol for neuromodulation by transcranial direct current stimulation(tDCS)remains unclear.Using the rotarod paradigm,we found that mouse motor learning was enhanced by anodal tDCS(3.2 mA/cm^(2))during but not before or after the performance of a task.Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS.Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner.Transcranial in vivo Ca^(2+)imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex(M1).Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance,suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement.Thus,application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.