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
Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain.In this disease,two different damage areas are identifying:the lesion core,in which cells ...Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain.In this disease,two different damage areas are identifying:the lesion core,in which cells quickly die;and the penumbra(surrounding the lesion core),in which cells are functionally weakened but may recover and restore their functions.The currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy,but they have a short therapeutic window(4.5 and 6 hours after stroke onset,respectively)and a low percentage of stroke patients actually receive these treatments.Memantine is an approved drug for the treatment of Alzheimer's disease.Memantine is a noncompetitive,low affinity and use-dependent antagonist of N-methyl-D-aspartate glutamate receptor.Memantine has several advantages over developing a new drug to treat focal ischemic stroke,but the most important is that it has sufficient safe probes in preclinical models and humans,and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair,this could help to increase the number of clinical trials.The present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models,to illustrate their potential to improve functional recovery in human patients.展开更多
Ischemic stroke causes brain inflammation and multi-organ injury,which is closely associated with the peroxisome proliferator-activated receptor-gamma(PPARγ)signaling pathway.Recent studies have indicated that ginsen...Ischemic stroke causes brain inflammation and multi-organ injury,which is closely associated with the peroxisome proliferator-activated receptor-gamma(PPARγ)signaling pathway.Recent studies have indicated that ginsenoside Rb1(GRb1)can protect the integrity of the blood-brain barrier after stroke.In the current study,a mouse model of middle cerebral artery occlusion/reperfusion(MCAO/R)was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγsignaling pathway.Staining(2,3,5-triphenyltetrazolium chloride,hematoxylin,and eosin)and Doppler ultrasonography were employed to detect pathological changes.Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs(tight junctions)and AJs(adherent junctions).Western blot and immunofluorescence were used to determine the levels of cell junction proteins,PPARγand NF-κB.Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular,pulmonary vascular,and intestinal epithelial connexins.In brain,lung,and intestinal tissues,GRb1 activated PPARγ,decreased the levels of phospho-NF-κB p65,and inhibited the production of proinflammatory cytokines,thereby maintaining barrier permeability.However,co-treatment with GRb1 and the PPARγantagonist GW9662 reversed the barrier-protective effect of GRb1.These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγpathway.展开更多
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.
文摘Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain.In this disease,two different damage areas are identifying:the lesion core,in which cells quickly die;and the penumbra(surrounding the lesion core),in which cells are functionally weakened but may recover and restore their functions.The currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy,but they have a short therapeutic window(4.5 and 6 hours after stroke onset,respectively)and a low percentage of stroke patients actually receive these treatments.Memantine is an approved drug for the treatment of Alzheimer's disease.Memantine is a noncompetitive,low affinity and use-dependent antagonist of N-methyl-D-aspartate glutamate receptor.Memantine has several advantages over developing a new drug to treat focal ischemic stroke,but the most important is that it has sufficient safe probes in preclinical models and humans,and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair,this could help to increase the number of clinical trials.The present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models,to illustrate their potential to improve functional recovery in human patients.
基金supported by the National Natural Science Foundation of China(Nos.81773971,82074058,82104438,and 82104437)the China Postdoctoral Science Foundation(Nos.2021M693518 and 2021M693519)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.SBK20210432 and SBK20210431)the National Science Foundation for the Third Batch of Special Funding for Postdoctoral Fellows(No.2021TQ0367)the“Double First-Class”University Project(No.CPU2018GF07)。
文摘Ischemic stroke causes brain inflammation and multi-organ injury,which is closely associated with the peroxisome proliferator-activated receptor-gamma(PPARγ)signaling pathway.Recent studies have indicated that ginsenoside Rb1(GRb1)can protect the integrity of the blood-brain barrier after stroke.In the current study,a mouse model of middle cerebral artery occlusion/reperfusion(MCAO/R)was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγsignaling pathway.Staining(2,3,5-triphenyltetrazolium chloride,hematoxylin,and eosin)and Doppler ultrasonography were employed to detect pathological changes.Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs(tight junctions)and AJs(adherent junctions).Western blot and immunofluorescence were used to determine the levels of cell junction proteins,PPARγand NF-κB.Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular,pulmonary vascular,and intestinal epithelial connexins.In brain,lung,and intestinal tissues,GRb1 activated PPARγ,decreased the levels of phospho-NF-κB p65,and inhibited the production of proinflammatory cytokines,thereby maintaining barrier permeability.However,co-treatment with GRb1 and the PPARγantagonist GW9662 reversed the barrier-protective effect of GRb1.These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγpathway.
