Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
BACKGROUND： Progressive ischemic stroke has higher fatality rate and disability rate than common cerebral infarction, thus it is very significant to investigate the early predicting factors related to the occurrence ...BACKGROUND： Progressive ischemic stroke has higher fatality rate and disability rate than common cerebral infarction, thus it is very significant to investigate the early predicting factors related to the occurrence of progressive ischemic stroke, the potential pathological mechanism and the risk factors of early intervention for preventing the occurrence of progressive ischemic stroke and ameliorating its outcome. OBJECTIVE： To analyze the possible related risk factors in patients with progressive ishcemic stroke, so as to provide reference for the prevention and treatment of progressive ishcemic stroke. DESIGN： A retrospective analysis. SETTING： Department of Neurology, General Hospital of Beijing Coal Mining Group. PARTICIPANTS： Totally 280 patients with progressive ischemic stroke were selected from the Department of Neurology, General Hospital of Beijing Coal Mining Group from March 2002 to June 2006, including 192 males and 88 females, with a mean age of （62±7） years old. They were all accorded with the diagnostic standards for cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995, and confired by CT or MRI, admitted within 24 hours after attack, and the neurological defect progressed gradually or aggravated in gradients within 72 hours after attack, and the aggravation of neurological defect was defined as the neurological deficit score decreased by more than 2 points. Meanwhile, 200 inpatients with non-progressive ischemic stroke （135 males and 65 females） were selected as the control group. METHODS： After admission, a univariate analysis of variance was conducted using the factors of blood pressure, history of diabetes mellitus, fever, leukocytosis, levels of blood lipids, fibrinogen, blood glucose and plasma homocysteine, cerebral arterial stenosis, and CT symptoms of early infarction, and the significant factors were involved in the multivariate non-conditional Logistic regression analysis. MAIN OUTCOME MEASURES： Results of the univariate analysis of variance of the factors related to progressive ischemic stroke; Results of the multivariate regression analysis. RESULTS： All the 480 patients were involved in the analysis of results. ① Results of the univariate analysis variance： There were significantly more patients with fever, leukocytosis, history of diabetes mellitus, cerebral arterial stenosis and CT symptoms of early infarction in the progressive ischemic stroke group than in the control group （P 〈 0.01）; The levels of blood glucose and fibrinogen in the progressive ischemic stroke group were significantly higher than those in the control group, while the level of blood pressure was significantly lower than that in the control group （P 〈 0.05 - 0.01）. ② Results of the multivariate Logistic regression analysis： The independent predicting factors for progressive ischemic stroke were history of diabetes mellitus, fever, leukocytosis, cerebral arterial stenosis, CT symptoms of early infarction, blood glucose and blood pressure （OR =2.61,2.96, 3.79, 1.03, 3.57, 2.68, 95% CI 0.92 - 3.59, P 〈 0.05 - 0.01）. CONCLUSION： History of diabetes mellitus, fever, leukocytosis, levels of blood pressure, blood glucose, cerebral arterial stenosis and CT symptoms of early infarction are the risk factors for progress ischemic stroke展开更多
OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activa...OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activated caspase-1 has thus been considered a promising target for stroke therapy.However,it remains not fully understood how caspase-1 ag⁃gravates progressive functional impairment.We previously identified a novel caspase-1 inhibitor CZL-80,the present study is to explore whether CZL-80 protects against progressive ischemic stroke.METHODS Male C57/BL6 mice and cas⁃pase-1-/-mice were subjected to photothrombotic(PT)-induced cerebral ischemia.CZL-80 was in⁃traperitoneally injected daily during 1-7 d,1-4 d,4-7 d after PT.The grid-walking task and the cyl⁃inder task were used to determine the motor function.RESULTS Mice developed primary and the secondary neurological dysfunction at 1 d and 4-7 d after PT onset.The activation of cas⁃pase-1 peaked at 7 d after ischemic stroke and caspase-1 was mainly derived from activated microglia.Treatment with CZL-80(30 mg·kg-1)during 1-7 d significantly improved motor func⁃tion.Administration of CZL-80 during 1-4 d could not ameliorate motor function loss while administration during 4-7 d after PT onset signifi⁃cantly reduced foot faults and forelimb symme⁃try.Remarkably,treatment with CZL-80 during 4-7 d showed no significant difference in efficacy compared with the its administration during 1-7 d,which indicated a key therapeutic window.More⁃over,the neuroprotective effect of CZL-80 during 4-7 d was available at least until 43 d after isch⁃emic stroke,indicating CZL-80 can improve the long-term neurological function after cerebral ischemia.Furthermore,administration of CZL-80(30 mg·kg-1)during 4-7 d after PT onset in cas⁃pase-1-/-mice failed to improve the motor func⁃tion,which suggested that the neuroprotective effect of CZL-80 was caspase-1-dependent.The results showed that CZL-80 did not inhibit the expression of GSDMD and failed to reduce neu⁃ronal loss after ischemia.These results indicated the effect of CZL-80 was not attributable to inhib⁃it pyroptosis.We further found that CZL-80 signif⁃icantly reduced the number of activated microglia in the peri-infarct brain cortex after ischemic stroke,which might be involved in its neuropro⁃tective effect.CONCLUSION CZL-80,a novel caspase-1 inhibitor,improved motor function after progressive ischemic stroke in mice.The effective therapeutic window of CZL-80 would be 4-7 d after ischemia,when the secondary neuro⁃logical dysfunction occurred.Therefore,the inter⁃vention by targeting caspase-1 in this window phase provides a novel strategy for the function⁃al recovery of stroke survivors.展开更多
MicroRNAs(miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. Micro RNA-29 b(mi R-29 b) plays a broad ...MicroRNAs(miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. Micro RNA-29 b(mi R-29 b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of mi R-29 b in animal and cell models by inhibiting mi R-29 b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg mi R-29 b antagomir was injected via the tail vein. Mi R-29 b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of mi R-29 b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of mi R-29 b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the mi R-29 antagomir for 48 hours. The results revealed that mi R-29 b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of mi R-29 b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University(approval No. 201709276 S) on September 27, 2017.展开更多
Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the...Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.展开更多
Ischemic stroke has high morbidity,mortality,disability rate and recurrence.It is the one of the main diseases that threaten people's health in China.Its etiology,pathogenesis,and reaction mechanism has been the r...Ischemic stroke has high morbidity,mortality,disability rate and recurrence.It is the one of the main diseases that threaten people's health in China.Its etiology,pathogenesis,and reaction mechanism has been the research hotspot and difficulty of related studies have shown that the optical coherence tomography technology is an effective measure to evaluate ischemic cerebral apoplexy.Optical coherence tomography(OCT)is a gradually developed and mature imaging technology in recent years,and there are related studies on internal carotid artery,retina and coronary artery.Based on the above background,this paper reviews the research progress of optical coherence tomography in the assessment of the etiology,pathogenesis and response mechanism of ischemic stroke.展开更多
Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomiza...Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomization method, 80 male SD rats were divided into normal group (n = 10), sham operation group (n = 24), model group (n = 23) and acupuncture group (n = 23). The normal group was bred routinely without any intervention. In the sham operation group, only the skin was cut to find and the nerves and blood vessels were stripped and sutured. The model group and the acupuncture group were sutured to prepare the MCAO model. After the model was successfully established, acupuncture of the acupuncture group rats was given once a day, and the needles were kept for 30 minutes each time. The rats in the sham operation group and the model group only imitated capture and return, and were treated with acupuncture for 2 consecutive courses, each course was 5 days, and the two courses were rested for 2 days. After that, Western blot was used to detect ERM, changes in the concentration of PI3K and Akt proteins. Results: Compared with the normal group, the expression levels of ERM, PI3K, and Akt proteins in the sham operation group were reduced. Compared with the sham operation group, the expression levels of ERM, PI3K, and Akt proteins in the model group were significantly down-regulated. Compared with the model group, the protein expression levels of ERM, PI3K and Akt were significantly up-regulated in the acupuncture group, and the difference was statistically significant (P < 0.05). Conclusion: Acupuncture can significantly up-regulate the expression of ERM, PI3K and Akt proteins, and its effect mechanism may be related to the transduction of ERM/PI3K/Akt signaling pathway in cells.展开更多
In recent years,the incidence of ischemic stroke has been increasing.Patients are prone to many complications after half a year of onset or has slow recovery of neuromotor function of one limb on one side of hemiplegi...In recent years,the incidence of ischemic stroke has been increasing.Patients are prone to many complications after half a year of onset or has slow recovery of neuromotor function of one limb on one side of hemiplegia.The clinical effect of acupuncture in treating this disease is remarkable.According to research,acupuncture combined with medication and rehabilitation can reduce the degree of nerve defects in the early stage of the disease,improve daily life,and improve prognosis.This article summarizes the research on acupuncture in the treatment of acute ischemic stroke for future reference.展开更多
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
文摘BACKGROUND： Progressive ischemic stroke has higher fatality rate and disability rate than common cerebral infarction, thus it is very significant to investigate the early predicting factors related to the occurrence of progressive ischemic stroke, the potential pathological mechanism and the risk factors of early intervention for preventing the occurrence of progressive ischemic stroke and ameliorating its outcome. OBJECTIVE： To analyze the possible related risk factors in patients with progressive ishcemic stroke, so as to provide reference for the prevention and treatment of progressive ishcemic stroke. DESIGN： A retrospective analysis. SETTING： Department of Neurology, General Hospital of Beijing Coal Mining Group. PARTICIPANTS： Totally 280 patients with progressive ischemic stroke were selected from the Department of Neurology, General Hospital of Beijing Coal Mining Group from March 2002 to June 2006, including 192 males and 88 females, with a mean age of （62±7） years old. They were all accorded with the diagnostic standards for cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995, and confired by CT or MRI, admitted within 24 hours after attack, and the neurological defect progressed gradually or aggravated in gradients within 72 hours after attack, and the aggravation of neurological defect was defined as the neurological deficit score decreased by more than 2 points. Meanwhile, 200 inpatients with non-progressive ischemic stroke （135 males and 65 females） were selected as the control group. METHODS： After admission, a univariate analysis of variance was conducted using the factors of blood pressure, history of diabetes mellitus, fever, leukocytosis, levels of blood lipids, fibrinogen, blood glucose and plasma homocysteine, cerebral arterial stenosis, and CT symptoms of early infarction, and the significant factors were involved in the multivariate non-conditional Logistic regression analysis. MAIN OUTCOME MEASURES： Results of the univariate analysis of variance of the factors related to progressive ischemic stroke; Results of the multivariate regression analysis. RESULTS： All the 480 patients were involved in the analysis of results. ① Results of the univariate analysis variance： There were significantly more patients with fever, leukocytosis, history of diabetes mellitus, cerebral arterial stenosis and CT symptoms of early infarction in the progressive ischemic stroke group than in the control group （P 〈 0.01）; The levels of blood glucose and fibrinogen in the progressive ischemic stroke group were significantly higher than those in the control group, while the level of blood pressure was significantly lower than that in the control group （P 〈 0.05 - 0.01）. ② Results of the multivariate Logistic regression analysis： The independent predicting factors for progressive ischemic stroke were history of diabetes mellitus, fever, leukocytosis, cerebral arterial stenosis, CT symptoms of early infarction, blood glucose and blood pressure （OR =2.61,2.96, 3.79, 1.03, 3.57, 2.68, 95% CI 0.92 - 3.59, P 〈 0.05 - 0.01）. CONCLUSION： History of diabetes mellitus, fever, leukocytosis, levels of blood pressure, blood glucose, cerebral arterial stenosis and CT symptoms of early infarction are the risk factors for progress ischemic stroke
文摘OBJECTIVE Progressive isch⁃emic stroke is characterized by aggravation of neurological dysfunction and poor prognosis.Neuroinflammation is involved in the pathological process of cerebral ischemia.Inflammasomes-activated caspase-1 has thus been considered a promising target for stroke therapy.However,it remains not fully understood how caspase-1 ag⁃gravates progressive functional impairment.We previously identified a novel caspase-1 inhibitor CZL-80,the present study is to explore whether CZL-80 protects against progressive ischemic stroke.METHODS Male C57/BL6 mice and cas⁃pase-1-/-mice were subjected to photothrombotic(PT)-induced cerebral ischemia.CZL-80 was in⁃traperitoneally injected daily during 1-7 d,1-4 d,4-7 d after PT.The grid-walking task and the cyl⁃inder task were used to determine the motor function.RESULTS Mice developed primary and the secondary neurological dysfunction at 1 d and 4-7 d after PT onset.The activation of cas⁃pase-1 peaked at 7 d after ischemic stroke and caspase-1 was mainly derived from activated microglia.Treatment with CZL-80(30 mg·kg-1)during 1-7 d significantly improved motor func⁃tion.Administration of CZL-80 during 1-4 d could not ameliorate motor function loss while administration during 4-7 d after PT onset signifi⁃cantly reduced foot faults and forelimb symme⁃try.Remarkably,treatment with CZL-80 during 4-7 d showed no significant difference in efficacy compared with the its administration during 1-7 d,which indicated a key therapeutic window.More⁃over,the neuroprotective effect of CZL-80 during 4-7 d was available at least until 43 d after isch⁃emic stroke,indicating CZL-80 can improve the long-term neurological function after cerebral ischemia.Furthermore,administration of CZL-80(30 mg·kg-1)during 4-7 d after PT onset in cas⁃pase-1-/-mice failed to improve the motor func⁃tion,which suggested that the neuroprotective effect of CZL-80 was caspase-1-dependent.The results showed that CZL-80 did not inhibit the expression of GSDMD and failed to reduce neu⁃ronal loss after ischemia.These results indicated the effect of CZL-80 was not attributable to inhib⁃it pyroptosis.We further found that CZL-80 signif⁃icantly reduced the number of activated microglia in the peri-infarct brain cortex after ischemic stroke,which might be involved in its neuropro⁃tective effect.CONCLUSION CZL-80,a novel caspase-1 inhibitor,improved motor function after progressive ischemic stroke in mice.The effective therapeutic window of CZL-80 would be 4-7 d after ischemia,when the secondary neuro⁃logical dysfunction occurred.Therefore,the inter⁃vention by targeting caspase-1 in this window phase provides a novel strategy for the function⁃al recovery of stroke survivors.
文摘MicroRNAs(miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. Micro RNA-29 b(mi R-29 b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of mi R-29 b in animal and cell models by inhibiting mi R-29 b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg mi R-29 b antagomir was injected via the tail vein. Mi R-29 b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of mi R-29 b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of mi R-29 b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the mi R-29 antagomir for 48 hours. The results revealed that mi R-29 b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of mi R-29 b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University(approval No. 201709276 S) on September 27, 2017.
基金supported by the National Institute of Neurological Disorders and Stroke under research grant NS088084(to HW)
文摘Ischemic stroke is a global epidemic condition due to an inadequate supply of blood and oxygen to a specific area of brain either by arterial blockage or by narrowing of blood vessels.Despite having advancement in the use of thrombolytic and clot removal medicine,significant numbers of stroke patients are still left out without option for treatment.In this review,we summarize recent research work on the activation ofδ-opioid receptor as a strategy for treating ischemic stroke-caused neuronal injury.Moreover,as activation ofδ-opioid receptor by a non-peptidicδ-opioid receptor agonist also modulates the expression,maturation and processing of amyloid precursor protein andβ-secretase activity,the potential role of these effects on ischemic stroke caused dementia or Alzheimer’s disease are also discussed.
基金supported by National Natural Science Foundation of China(No.81860238)Key R&D Project of Hainan Province(No.ZDYF2018233)。
文摘Ischemic stroke has high morbidity,mortality,disability rate and recurrence.It is the one of the main diseases that threaten people's health in China.Its etiology,pathogenesis,and reaction mechanism has been the research hotspot and difficulty of related studies have shown that the optical coherence tomography technology is an effective measure to evaluate ischemic cerebral apoplexy.Optical coherence tomography(OCT)is a gradually developed and mature imaging technology in recent years,and there are related studies on internal carotid artery,retina and coronary artery.Based on the above background,this paper reviews the research progress of optical coherence tomography in the assessment of the etiology,pathogenesis and response mechanism of ischemic stroke.
文摘Objective: To observe the effect of acupuncture on the expression of ERM/PI3K/Akt signaling pathway in the brain tissue around the infarct focus of ischemic stroke model rats. Methods: According to the block randomization method, 80 male SD rats were divided into normal group (n = 10), sham operation group (n = 24), model group (n = 23) and acupuncture group (n = 23). The normal group was bred routinely without any intervention. In the sham operation group, only the skin was cut to find and the nerves and blood vessels were stripped and sutured. The model group and the acupuncture group were sutured to prepare the MCAO model. After the model was successfully established, acupuncture of the acupuncture group rats was given once a day, and the needles were kept for 30 minutes each time. The rats in the sham operation group and the model group only imitated capture and return, and were treated with acupuncture for 2 consecutive courses, each course was 5 days, and the two courses were rested for 2 days. After that, Western blot was used to detect ERM, changes in the concentration of PI3K and Akt proteins. Results: Compared with the normal group, the expression levels of ERM, PI3K, and Akt proteins in the sham operation group were reduced. Compared with the sham operation group, the expression levels of ERM, PI3K, and Akt proteins in the model group were significantly down-regulated. Compared with the model group, the protein expression levels of ERM, PI3K and Akt were significantly up-regulated in the acupuncture group, and the difference was statistically significant (P < 0.05). Conclusion: Acupuncture can significantly up-regulate the expression of ERM, PI3K and Akt proteins, and its effect mechanism may be related to the transduction of ERM/PI3K/Akt signaling pathway in cells.
基金Key Laboratory of Fang’s Head Acupuncture,Shaanxi Administration of Traditional Chinese Medicine,Shaanxi Traditional Chinese Medicine Fa([2018]No.32)Key Scientific Research Project of Traditional Chinese Medicine Inheritance and Innovation and Development of"Qin Medicine"of Shaanxi Administration of Traditional Chinese Medicine,2021-01-22-007。
文摘In recent years,the incidence of ischemic stroke has been increasing.Patients are prone to many complications after half a year of onset or has slow recovery of neuromotor function of one limb on one side of hemiplegia.The clinical effect of acupuncture in treating this disease is remarkable.According to research,acupuncture combined with medication and rehabilitation can reduce the degree of nerve defects in the early stage of the disease,improve daily life,and improve prognosis.This article summarizes the research on acupuncture in the treatment of acute ischemic stroke for future reference.
