The present study aimed to improve the processing of data acquired from laser speckle contrast imaging(LSCI) to provide a standardization method to explore changes in regional cerebral blood flow(r CBF) and to det...The present study aimed to improve the processing of data acquired from laser speckle contrast imaging(LSCI) to provide a standardization method to explore changes in regional cerebral blood flow(r CBF) and to determine the correlations among r CBF, cerebral ischemic lesion volume and microvascular density over time in a focal ischemic region. C57BL/6J mice were subjected to focal photothrombotic(PT) ischemia. r CBF was measured using LSCI at different time points before and after PT ischemia through an intact skull. Standardized r CBF(Sr CBF), defined as the ratio of r CBF measured in the ipsilateral region of interest(ROI) to that in the corresponding contralateral region, was calculated to evaluate potential changes. In addition, the volume of the ischemic lesion and the microvascular density were determined using Nissl staining and immunofluorescence, respectively. The relationships among the ischemic lesion volume, microvascular density and Sr CBF were analyzed over time. The results showed that the cortical r CBF measured using LSCI following PT ischemia in the C57BL/6J mice gradually increased. Changes in the cerebral ischemic lesion volume were negatively correlated with Sr CBF in the ischemic region. Changes in the microvascular density were similar to those observed in Sr CBF. Our findings indicate that LSCI is a practical technique for observing changes in murine cortical r CBF without skull opening and for analyzing the relationships among the ischemic lesion volume, microvascular density and Sr CBF following focal cerebral ischemia. Preliminary results also suggest that the use of LSCI to observe the formation of collateral circulation is feasible.展开更多
Focal ischemia due to reduction of cerebral blood flow(CBF),creates 2 zones of damage:the core area,which suffers severe damage,and penumbra area,which surrounds the core and suffers intermediate levels of injury.Obje...Focal ischemia due to reduction of cerebral blood flow(CBF),creates 2 zones of damage:the core area,which suffers severe damage,and penumbra area,which surrounds the core and suffers intermediate levels of injury.Objectives:A novel method is introduced,which evaluates mitochondrial function in the core and in the penumbra,during focal cerebral ischemia.Methods:Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion(MCAO)for 60 minutes,followed by 60 minutes of reperfusion.Mitochondrial function was assessed by a unique Multi-Site—Multi-Parametric(MSMP)monitoring system,which measures mitochondrial NADH using fluorometric technique,and CBF using Laser Doppler Flowmetry(LDF).Results:At the onset of occlusion,CBF dropped and NADH increased significantly only in the right hemisphere.CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra.After reperfusion,CBF and NADH recovered correspondingly to the intensity of ischemia.Conclusion:Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions,with an emphasis on mitochondrial function.展开更多
1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effe...1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemiain vivo, and a rabbit model of isolated basilar arteriesin vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flowin vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in thein vitro rabbit model. DDPH (3 × 10–5 M) also inhibited histamine-stimulated extracellular calcium inlfux and intracellular calcium release. Our ifndings suggest that DDPH has a vasodilative effect bothin vivo andin vitro, which mediates a neuropro-tective effect on ischemic nerve tissue.展开更多
Nerve cell metabolism in post brain ischemia depends on increased microcirculation perfusion and transport function of microvascular endothelial cells. In the present study, a rat model of middle cerebral artery occlu...Nerve cell metabolism in post brain ischemia depends on increased microcirculation perfusion and transport function of microvascular endothelial cells. In the present study, a rat model of middle cerebral artery occlusion was established to investigate the influence of electroacupuncture (EA) on hippocampal CA1 cerebral blood flow and glucose transporter 1 (GLUT1) expression in the microvascular endothelial cells. Following EA at Neiguan (PC 6), the cerebral blood flow in the ischemic hippocampal CA1 region was significantly elevated, the number and microvascular integrated absorbance of the GLUTl-positive cells were significantly increased, nerve cell damage was ameliorated, and GLUT1 protein expression in the ischemic hippocampus was significantly increased. Results demonstrate that EA increased the cerebral blood flow of the hippocampal CA1 region and improved the glucose transport function, thereby attenuating neuronal injuries.展开更多
Excess production of reactive oxygen species (ROS) critically contributes to occurrence of reperfusion injury, the paradoxical response of ischemic brain tissue to restoration of cerebral blood flow. However, the en...Excess production of reactive oxygen species (ROS) critically contributes to occurrence of reperfusion injury, the paradoxical response of ischemic brain tissue to restoration of cerebral blood flow. However, the enzymatic sources of ROS generation remain to be unclear. This study examined Nox2-ontaining NADPH oxidase (Nox2) expression and its activity in ischemic brain tissue following post-ischemic reperfusion to clarify the mechanism of enzymatic reaction of ROS. Male Sprague-Dawley rats were subjected to 90-minute middle cerebral artery occlusion, followed by 3 or 22.5 hours of reperfusion. Quantitative reverse transcriptase PCR and western blot assay were performed to measure mRNA and protein expression of Nox2. Lucigenin fluorescence assays were performed to assess Nox activity. Our data showed that Nox2 mRNA and protein expression levels were significantly increased (3.7-fold for mRNA and 3.6-fold for protein) in ischemic brain tissue at 22.5 hours but not at 3 hours following post-ischemic reperfusion. Similar results were obtained for the changes of NADPH oxidase activity in ischemic cerebral tissue at the two reperfusion time points. Our results suggest that Nox2 may not contribute to the early burst of reperfusion-related ROS generation, but is rather an important source of ROS generation during prolonged reperfusion.展开更多
目的 探讨急性缺血性脑卒中(acute ischemic stroke, AIS)患者溶栓后脑血流与缺血再灌注损伤及神经功能的相关性。方法 回顾性选取2021年2月至2024年2月唐山市工人医院神经内科收治的AIS患者150例,根据溶栓后CT灌注成像检查患侧脑血流量...目的 探讨急性缺血性脑卒中(acute ischemic stroke, AIS)患者溶栓后脑血流与缺血再灌注损伤及神经功能的相关性。方法 回顾性选取2021年2月至2024年2月唐山市工人医院神经内科收治的AIS患者150例,根据溶栓后CT灌注成像检查患侧脑血流量(cerebral blood flow, CBF)变化情况分为高灌注组48例和低灌注组102例。获取出血转化情况及灌注参数资料,后者包括CBF、脑血容量(cerebral blood volume, CBV)、残余功能达峰时间(time to maximum of the residual function, T_(max))、平均通过时间(mean transit time, MTT)和达峰时间(time to peak, TTP),以及相对值rCBF、rCBV、T_(r, max)、rMTT及rTTP。比较2组一般临床资料、氧化应激、美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分和炎性因子水平。采用Pearson/Spearman相关性分析AIS患者溶栓后rCBF与氧化应激、炎性因子、出血转化情况及NIHSS评分的相关性。结果 低灌注组患侧MTT、T_(max)、TTP显著高于健侧,CBF显著低于健侧,差异有统计学意义(P<0.01)。高灌注组患侧MTT、TTP显著低于健侧,CBF、CBV显著高于健侧,差异有统计学意义(P<0.01)。低灌注组rMTT、T_(r, max)、rTTP显著高于高灌注组,rCBF、rCBV显著低于高灌注组(P<0.01)。低灌注组丙二醛、晚期氧化蛋白产物、肿瘤坏死因子α、C反应蛋白水平显著低于高灌注组,超氧化物歧化酶水平显著高于高灌注组,差异有统计学意义(P<0.05,P<0.01)。Pearson相关性分析显示,rCBF与丙二醛、肿瘤坏死因子α呈负相关(r=-0.436,P<0.01;r=-0.451,P<0.01),与超氧化物歧化酶呈正相关(r=0.412,P<0.01)。结论 AIS患者溶栓后脑血流变化与缺血再灌注损伤存在较好相关性,但与神经功能恢复情况不具备显著相关性。展开更多
OBJECTIVE: To identify global research trends in the use of acupuncture to treat cerebral infarction. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of acupuncture to treat cerebral infar...OBJECTIVE: To identify global research trends in the use of acupuncture to treat cerebral infarction. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of acupuncture to treat cerebral infarction published during 2002-2011, retrieved from Scopus, using the key words of acupuncture and cerebral infarction or ischemic stroke. SELECTION CRITERIA: Inclusion criteria: peer-reviewed articles on the use of acupuncture to treat cerebral infarction indexed in Scopus and published between 2002 and 2011; types of publications were original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles that required manual searching or telephone access; documents that were not published in the public domain; and corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) language of publication; (c) type of publication; (d) key words of publication; (e) publication by research field; (f) publication by journal (g) publication by country and institution; (h) publication by author; (i) most-cited papers between 2002 and 2006; and (j) most-cited papers between 2007 and 2011. RESULTS: A total of 160 publications on the use of acupuncture to treat cerebral infarction from 2002-2011 were retrieved from Scopus. The number of publications increased gradually over the 10-year study period; most were written in Chinese or English. Articles and reviews constituted the major types. The most frequent key word used was acupuncture. The most prolific journals in this area were Zhongguo 7hen Jiu and the Chinese Journal of Clinical Rehabilitation. Of the 160 publications retrieved, half came from Chinese authors and institutions. Tianjin University of Traditional Chinese Medicine was the most prolific research institute. Two papers were cited 30 times; they were published in 2002 and 2009, respectively. CONCLUSION: In the field of neuroscience, there is little literature on acupuncture for cerebral infarction. The most-cited papers were cited 30 times in the past 3 years. We believe that, with advances in the study of mechanisms in neurobiology, research on acupuncture will also advance and will become the concern of more scholars.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
基金supported by the National Natural Science Foundation of China(No.81271407)
文摘The present study aimed to improve the processing of data acquired from laser speckle contrast imaging(LSCI) to provide a standardization method to explore changes in regional cerebral blood flow(r CBF) and to determine the correlations among r CBF, cerebral ischemic lesion volume and microvascular density over time in a focal ischemic region. C57BL/6J mice were subjected to focal photothrombotic(PT) ischemia. r CBF was measured using LSCI at different time points before and after PT ischemia through an intact skull. Standardized r CBF(Sr CBF), defined as the ratio of r CBF measured in the ipsilateral region of interest(ROI) to that in the corresponding contralateral region, was calculated to evaluate potential changes. In addition, the volume of the ischemic lesion and the microvascular density were determined using Nissl staining and immunofluorescence, respectively. The relationships among the ischemic lesion volume, microvascular density and Sr CBF were analyzed over time. The results showed that the cortical r CBF measured using LSCI following PT ischemia in the C57BL/6J mice gradually increased. Changes in the cerebral ischemic lesion volume were negatively correlated with Sr CBF in the ischemic region. Changes in the microvascular density were similar to those observed in Sr CBF. Our findings indicate that LSCI is a practical technique for observing changes in murine cortical r CBF without skull opening and for analyzing the relationships among the ischemic lesion volume, microvascular density and Sr CBF following focal cerebral ischemia. Preliminary results also suggest that the use of LSCI to observe the formation of collateral circulation is feasible.
文摘Focal ischemia due to reduction of cerebral blood flow(CBF),creates 2 zones of damage:the core area,which suffers severe damage,and penumbra area,which surrounds the core and suffers intermediate levels of injury.Objectives:A novel method is introduced,which evaluates mitochondrial function in the core and in the penumbra,during focal cerebral ischemia.Methods:Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion(MCAO)for 60 minutes,followed by 60 minutes of reperfusion.Mitochondrial function was assessed by a unique Multi-Site—Multi-Parametric(MSMP)monitoring system,which measures mitochondrial NADH using fluorometric technique,and CBF using Laser Doppler Flowmetry(LDF).Results:At the onset of occlusion,CBF dropped and NADH increased significantly only in the right hemisphere.CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra.After reperfusion,CBF and NADH recovered correspondingly to the intensity of ischemia.Conclusion:Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions,with an emphasis on mitochondrial function.
基金financially supported by grants from the National Natural Science Foundation of China,No.81173038Yangtz River Navigational Matters Authority of Ministry of Transport of China,No.201210011Clinical Medicine Research Program of Wuhan Health Planning Commission of China,No.WX14D12
文摘1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemiain vivo, and a rabbit model of isolated basilar arteriesin vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flowin vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in thein vitro rabbit model. DDPH (3 × 10–5 M) also inhibited histamine-stimulated extracellular calcium inlfux and intracellular calcium release. Our ifndings suggest that DDPH has a vasodilative effect bothin vivo andin vitro, which mediates a neuropro-tective effect on ischemic nerve tissue.
基金the National Natural Science Foundation of China,No. 30672717
文摘Nerve cell metabolism in post brain ischemia depends on increased microcirculation perfusion and transport function of microvascular endothelial cells. In the present study, a rat model of middle cerebral artery occlusion was established to investigate the influence of electroacupuncture (EA) on hippocampal CA1 cerebral blood flow and glucose transporter 1 (GLUT1) expression in the microvascular endothelial cells. Following EA at Neiguan (PC 6), the cerebral blood flow in the ischemic hippocampal CA1 region was significantly elevated, the number and microvascular integrated absorbance of the GLUTl-positive cells were significantly increased, nerve cell damage was ameliorated, and GLUT1 protein expression in the ischemic hippocampus was significantly increased. Results demonstrate that EA increased the cerebral blood flow of the hippocampal CA1 region and improved the glucose transport function, thereby attenuating neuronal injuries.
基金financially supported by grants from Shenzhen Science and Technology Innovation Commission of China,No.JCYJ20150330102401097,KQCX20140521101427034,JCYJ20140414170821291China Postdoctoral Science Foundation,No.2015M572388
文摘Excess production of reactive oxygen species (ROS) critically contributes to occurrence of reperfusion injury, the paradoxical response of ischemic brain tissue to restoration of cerebral blood flow. However, the enzymatic sources of ROS generation remain to be unclear. This study examined Nox2-ontaining NADPH oxidase (Nox2) expression and its activity in ischemic brain tissue following post-ischemic reperfusion to clarify the mechanism of enzymatic reaction of ROS. Male Sprague-Dawley rats were subjected to 90-minute middle cerebral artery occlusion, followed by 3 or 22.5 hours of reperfusion. Quantitative reverse transcriptase PCR and western blot assay were performed to measure mRNA and protein expression of Nox2. Lucigenin fluorescence assays were performed to assess Nox activity. Our data showed that Nox2 mRNA and protein expression levels were significantly increased (3.7-fold for mRNA and 3.6-fold for protein) in ischemic brain tissue at 22.5 hours but not at 3 hours following post-ischemic reperfusion. Similar results were obtained for the changes of NADPH oxidase activity in ischemic cerebral tissue at the two reperfusion time points. Our results suggest that Nox2 may not contribute to the early burst of reperfusion-related ROS generation, but is rather an important source of ROS generation during prolonged reperfusion.
文摘目的 探讨急性缺血性脑卒中(acute ischemic stroke, AIS)患者溶栓后脑血流与缺血再灌注损伤及神经功能的相关性。方法 回顾性选取2021年2月至2024年2月唐山市工人医院神经内科收治的AIS患者150例,根据溶栓后CT灌注成像检查患侧脑血流量(cerebral blood flow, CBF)变化情况分为高灌注组48例和低灌注组102例。获取出血转化情况及灌注参数资料,后者包括CBF、脑血容量(cerebral blood volume, CBV)、残余功能达峰时间(time to maximum of the residual function, T_(max))、平均通过时间(mean transit time, MTT)和达峰时间(time to peak, TTP),以及相对值rCBF、rCBV、T_(r, max)、rMTT及rTTP。比较2组一般临床资料、氧化应激、美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分和炎性因子水平。采用Pearson/Spearman相关性分析AIS患者溶栓后rCBF与氧化应激、炎性因子、出血转化情况及NIHSS评分的相关性。结果 低灌注组患侧MTT、T_(max)、TTP显著高于健侧,CBF显著低于健侧,差异有统计学意义(P<0.01)。高灌注组患侧MTT、TTP显著低于健侧,CBF、CBV显著高于健侧,差异有统计学意义(P<0.01)。低灌注组rMTT、T_(r, max)、rTTP显著高于高灌注组,rCBF、rCBV显著低于高灌注组(P<0.01)。低灌注组丙二醛、晚期氧化蛋白产物、肿瘤坏死因子α、C反应蛋白水平显著低于高灌注组,超氧化物歧化酶水平显著高于高灌注组,差异有统计学意义(P<0.05,P<0.01)。Pearson相关性分析显示,rCBF与丙二醛、肿瘤坏死因子α呈负相关(r=-0.436,P<0.01;r=-0.451,P<0.01),与超氧化物歧化酶呈正相关(r=0.412,P<0.01)。结论 AIS患者溶栓后脑血流变化与缺血再灌注损伤存在较好相关性,但与神经功能恢复情况不具备显著相关性。
文摘OBJECTIVE: To identify global research trends in the use of acupuncture to treat cerebral infarction. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of acupuncture to treat cerebral infarction published during 2002-2011, retrieved from Scopus, using the key words of acupuncture and cerebral infarction or ischemic stroke. SELECTION CRITERIA: Inclusion criteria: peer-reviewed articles on the use of acupuncture to treat cerebral infarction indexed in Scopus and published between 2002 and 2011; types of publications were original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles that required manual searching or telephone access; documents that were not published in the public domain; and corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) language of publication; (c) type of publication; (d) key words of publication; (e) publication by research field; (f) publication by journal (g) publication by country and institution; (h) publication by author; (i) most-cited papers between 2002 and 2006; and (j) most-cited papers between 2007 and 2011. RESULTS: A total of 160 publications on the use of acupuncture to treat cerebral infarction from 2002-2011 were retrieved from Scopus. The number of publications increased gradually over the 10-year study period; most were written in Chinese or English. Articles and reviews constituted the major types. The most frequent key word used was acupuncture. The most prolific journals in this area were Zhongguo 7hen Jiu and the Chinese Journal of Clinical Rehabilitation. Of the 160 publications retrieved, half came from Chinese authors and institutions. Tianjin University of Traditional Chinese Medicine was the most prolific research institute. Two papers were cited 30 times; they were published in 2002 and 2009, respectively. CONCLUSION: In the field of neuroscience, there is little literature on acupuncture for cerebral infarction. The most-cited papers were cited 30 times in the past 3 years. We believe that, with advances in the study of mechanisms in neurobiology, research on acupuncture will also advance and will become the concern of more scholars.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.