Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of ...Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra.Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR.Therefore,this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra.Rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion.Cerebral infarct volume was measured using 2%TTC staining.TUNEL staining was conducted to evaluate neuronal apoptosis.Western blotting and immunohistochemistry were used to detect the proteins involved in the JAK2/STAT3/PI3K/AKT/mTOR pathway.The results suggested that resveratrol significantly improved neurological function,reduced cerebral infarct volume,decreased neuronal damage,and markedly attenuated neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.These results suggested that resveratrol provides a neuroprotective effect against cerebral ischemia/reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3.展开更多
Background：Intravoxel incoherent motion （IVIM） has the potential to provide both diffusion and perfusion information without an exogenous contrast agent,its application for the brain is promising,however,feasibilit...Background：Intravoxel incoherent motion （IVIM） has the potential to provide both diffusion and perfusion information without an exogenous contrast agent,its application for the brain is promising,however,feasibility studies on this are relatively scarce.The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke （AIS）.Methods：Patients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset.Fifteen patients （mean age was 68.7 ± 8.0 years） who underwent arterial spin labeling （ASL） and diffusion-weighted imaging （DWI） were identified as having AIS with ischemic penumbra were enrolled,where ischemic penumbra referred to the mismatch areas of ASL and DWI.Eleven different b-values were applied in the biexponential model.Regions of interest were selected in ischemic penumbras and contralateral normal brain regions.Fast apparent diffusion coefficients （ADCs） and ASL cerebral blood flow （CBF） were measured.The paired t-test was applied to compare ASL CBF,fast ADC,and slow ADC measurements between ischemic penumbras and contralateral normal brain regions.Linear regression and Pearson＇s correlation were used to evaluate the correlations among quantitative results.Results：The fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions （1.93 ± 0.78 μm2/ms vs.3.97 ± 2.49 μm2/ms,P =0.007;13.5 ± 4.5 ml· 100 g-1 ·min-1 vs.29.1 ± 12.7 ml·100 g-1 ·min-1,P ＜ 0.001,respectively）.No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions （0.203 ± 0.090 μm2/ms vs.0.198 ± 0.100 μm2/ms,P =0.451）.Compared with contralateral normal brain regions,both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same.A significant correlation was detected between fast ADCs and ASL CBFs （r =0.416,P ＜ 0.05）.No statistically significant correlation was obse展开更多
In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes （T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]） follow...In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes （T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]） following cerebral infarction. The pathological changes were divided into three phases： early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase （less than 2 hours post-infarction）, there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase （2-4 hours post-infarction）, a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase （4-6 hours post-infarction）, significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients （10/51） had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients （8/35） had an onset time less than 6 hours. These data suggest that defining the ＂therapeutic time window＂ as 展开更多
目的探讨低氧预适应(HPC)对脑中动脉阻塞(MCAO)所致脑缺血性损伤的影响及其可能机制。方法借助已建小鼠整体HPC和脑MCAO模型,应用2,3,5氯-化三苯基四氮唑(TTC)染色、神经行为学评分、SDS-PAGE和W estern b lot等技术方法,观察脑梗死面...目的探讨低氧预适应(HPC)对脑中动脉阻塞(MCAO)所致脑缺血性损伤的影响及其可能机制。方法借助已建小鼠整体HPC和脑MCAO模型,应用2,3,5氯-化三苯基四氮唑(TTC)染色、神经行为学评分、SDS-PAGE和W estern b lot等技术方法,观察脑梗死面积、水肿率、行为学,以及脑梗死核心和半影区新奇型蛋白激酶C(nPKC)膜转位的变化。结果MCAO可诱发小鼠脑皮层、海马和丘脑(由于发生率很低,数据未统计)等3种典型缺血模式;在皮层缺血模式中,HPC明显减小脑梗死面积(P<0.05,n=12)、缺血区吸光度值(P<0.05,n=12)和水肿率(P<0.05,n=12);而在海马缺血模式上,HPC只明显降低海马梗死区吸光度值(P<0.05,n=12);HPC可在一定程度上缓解MCAO小鼠的行为学改变;此外,HPC可缓解MCAO所致皮层缺血半影区nPKC膜转位水平的降低。结论HPC降低MCAO所致脑缺血性损伤,且nPKC可能参与了这种保护作用。展开更多
AIM:To review the literature on the assessment of venous vessels to estimate the penumbra on T2*w imaging and susceptibility-weighted imaging (SWI). METHODS:Literature that reported on the assessment of penumbra by T2...AIM:To review the literature on the assessment of venous vessels to estimate the penumbra on T2*w imaging and susceptibility-weighted imaging (SWI). METHODS:Literature that reported on the assessment of penumbra by T2*w imaging or SWI and used a validation method was included. PubMed and relevant stroke and magnetic resonance imaging (MRI) related conference abstracts were searched. Abstracts that had overlapping content with full text articles were excluded. The retrieved literature was scanned for further relevant references. Only clinical literature published in English was considered, patients with Moya-Moya syndrome were disregarded. Data is given as cumulative absolute and relative values, ranges are given where appropriate. RESULTS:Forty-three publications including 1145 patients could be identified. T2*w imaging was used in 16 publications (627 patients), SWI in 26 publications (453 patients). Only one publication used both (65 patients). The cumulative presence of hypointense vessel sign was 54% (range 32%-100%) for T2* (668 patients) and 81% (range 34%-100%) for SWI (334 patients). There was rare mentioning of interrater agreement (6 publications, 210 patients) and reliability (1 publication, 20 patients) but the numbers reported ranged from good to excellent. In most publications (n = 22) perfusion MRI was used as a validation method (617 patients). More patients were scanned in the subacute than in the acute phase (596 patients vs 320 patients). Clinical outcome was reported in 13 publications (521 patients) but was not consistent. CONCLUSION:The low presence of vessels signs on T2*w imaging makes SWI much more promising. More research is needed to obtain formal validation and quantification.展开更多
The concept of magnetic resonance perfusion-diffusion mismatch(PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stro... The concept of magnetic resonance perfusion-diffusion mismatch(PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stroke in animals and patients.Recent studies demonstrated that PDM does not optimally define the ischemic penumbra;because early abnormality on diffusion-weighted imaging overestimates the infarct core by including part of the penumbra,and the abnormality on perfusion weighted imaging overestimates the penumbra by including regions of benign oligemia.To overcome these limitations,many efforts have been made to optimize conventional PDM.Various alternatives beyond the PDM concept are under investigation in order to better define the penumbra.The PDM theory has been applied in ischemic stroke for at least three purposes:to be used as a practical selection tool for stroke treatment;to test the hypothesis that patients with PDM pattern will benefit from treatment,while those without mismatch pattern will not;to be a surrogate measure for stroke outcome.The main patterns of PDM and its relation with clinical outcomes were also briefly reviewed.The conclusion was that patients with PDM documented more reperfusion,reduced infarct growth and better clinical outcomes compared to patients without PDM,but it was not yet clear that thrombolytic therapy is beneficial when patients were selected on PDM.Studies based on a larger cohort are currently under investigation to further validate the PDM hypothesis.展开更多
Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress pathways.Few studies have examined the endoplasmic reticulum-me...Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress pathways.Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury,and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra.Here,we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12,caspase-3 and the endoplasmic reticulum stress marker 78 k Da glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours.Furthermore,numbers of terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury.These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra,and may play an important role in the pathophysiology of secondary brain injury.展开更多
基金supported by the Foundation for Science and Technology Research Project of Chongqing(cstc2012ggB1002).
文摘Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra.Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR.Therefore,this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra.Rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion.Cerebral infarct volume was measured using 2%TTC staining.TUNEL staining was conducted to evaluate neuronal apoptosis.Western blotting and immunohistochemistry were used to detect the proteins involved in the JAK2/STAT3/PI3K/AKT/mTOR pathway.The results suggested that resveratrol significantly improved neurological function,reduced cerebral infarct volume,decreased neuronal damage,and markedly attenuated neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.These results suggested that resveratrol provides a neuroprotective effect against cerebral ischemia/reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3.
文摘Background：Intravoxel incoherent motion （IVIM） has the potential to provide both diffusion and perfusion information without an exogenous contrast agent,its application for the brain is promising,however,feasibility studies on this are relatively scarce.The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke （AIS）.Methods：Patients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset.Fifteen patients （mean age was 68.7 ± 8.0 years） who underwent arterial spin labeling （ASL） and diffusion-weighted imaging （DWI） were identified as having AIS with ischemic penumbra were enrolled,where ischemic penumbra referred to the mismatch areas of ASL and DWI.Eleven different b-values were applied in the biexponential model.Regions of interest were selected in ischemic penumbras and contralateral normal brain regions.Fast apparent diffusion coefficients （ADCs） and ASL cerebral blood flow （CBF） were measured.The paired t-test was applied to compare ASL CBF,fast ADC,and slow ADC measurements between ischemic penumbras and contralateral normal brain regions.Linear regression and Pearson＇s correlation were used to evaluate the correlations among quantitative results.Results：The fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions （1.93 ± 0.78 μm2/ms vs.3.97 ± 2.49 μm2/ms,P =0.007;13.5 ± 4.5 ml· 100 g-1 ·min-1 vs.29.1 ± 12.7 ml·100 g-1 ·min-1,P ＜ 0.001,respectively）.No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions （0.203 ± 0.090 μm2/ms vs.0.198 ± 0.100 μm2/ms,P =0.451）.Compared with contralateral normal brain regions,both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same.A significant correlation was detected between fast ADCs and ASL CBFs （r =0.416,P ＜ 0.05）.No statistically significant correlation was obse
基金supported by the National Natural Science Foundation of China,No.30960399,and No.81160181
文摘In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes （T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]） following cerebral infarction. The pathological changes were divided into three phases： early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase （less than 2 hours post-infarction）, there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase （2-4 hours post-infarction）, a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase （4-6 hours post-infarction）, significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients （10/51） had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients （8/35） had an onset time less than 6 hours. These data suggest that defining the ＂therapeutic time window＂ as
文摘目的探讨低氧预适应(HPC)对脑中动脉阻塞(MCAO)所致脑缺血性损伤的影响及其可能机制。方法借助已建小鼠整体HPC和脑MCAO模型,应用2,3,5氯-化三苯基四氮唑(TTC)染色、神经行为学评分、SDS-PAGE和W estern b lot等技术方法,观察脑梗死面积、水肿率、行为学,以及脑梗死核心和半影区新奇型蛋白激酶C(nPKC)膜转位的变化。结果MCAO可诱发小鼠脑皮层、海马和丘脑(由于发生率很低,数据未统计)等3种典型缺血模式;在皮层缺血模式中,HPC明显减小脑梗死面积(P<0.05,n=12)、缺血区吸光度值(P<0.05,n=12)和水肿率(P<0.05,n=12);而在海马缺血模式上,HPC只明显降低海马梗死区吸光度值(P<0.05,n=12);HPC可在一定程度上缓解MCAO小鼠的行为学改变;此外,HPC可缓解MCAO所致皮层缺血半影区nPKC膜转位水平的降低。结论HPC降低MCAO所致脑缺血性损伤,且nPKC可能参与了这种保护作用。
文摘AIM:To review the literature on the assessment of venous vessels to estimate the penumbra on T2*w imaging and susceptibility-weighted imaging (SWI). METHODS:Literature that reported on the assessment of penumbra by T2*w imaging or SWI and used a validation method was included. PubMed and relevant stroke and magnetic resonance imaging (MRI) related conference abstracts were searched. Abstracts that had overlapping content with full text articles were excluded. The retrieved literature was scanned for further relevant references. Only clinical literature published in English was considered, patients with Moya-Moya syndrome were disregarded. Data is given as cumulative absolute and relative values, ranges are given where appropriate. RESULTS:Forty-three publications including 1145 patients could be identified. T2*w imaging was used in 16 publications (627 patients), SWI in 26 publications (453 patients). Only one publication used both (65 patients). The cumulative presence of hypointense vessel sign was 54% (range 32%-100%) for T2* (668 patients) and 81% (range 34%-100%) for SWI (334 patients). There was rare mentioning of interrater agreement (6 publications, 210 patients) and reliability (1 publication, 20 patients) but the numbers reported ranged from good to excellent. In most publications (n = 22) perfusion MRI was used as a validation method (617 patients). More patients were scanned in the subacute than in the acute phase (596 patients vs 320 patients). Clinical outcome was reported in 13 publications (521 patients) but was not consistent. CONCLUSION:The low presence of vessels signs on T2*w imaging makes SWI much more promising. More research is needed to obtain formal validation and quantification.
文摘 The concept of magnetic resonance perfusion-diffusion mismatch(PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stroke in animals and patients.Recent studies demonstrated that PDM does not optimally define the ischemic penumbra;because early abnormality on diffusion-weighted imaging overestimates the infarct core by including part of the penumbra,and the abnormality on perfusion weighted imaging overestimates the penumbra by including regions of benign oligemia.To overcome these limitations,many efforts have been made to optimize conventional PDM.Various alternatives beyond the PDM concept are under investigation in order to better define the penumbra.The PDM theory has been applied in ischemic stroke for at least three purposes:to be used as a practical selection tool for stroke treatment;to test the hypothesis that patients with PDM pattern will benefit from treatment,while those without mismatch pattern will not;to be a surrogate measure for stroke outcome.The main patterns of PDM and its relation with clinical outcomes were also briefly reviewed.The conclusion was that patients with PDM documented more reperfusion,reduced infarct growth and better clinical outcomes compared to patients without PDM,but it was not yet clear that thrombolytic therapy is beneficial when patients were selected on PDM.Studies based on a larger cohort are currently under investigation to further validate the PDM hypothesis.
基金supported by the Natural Science Foundation of Hebei Province of China,No.H2014206383Foundation for High-Level Personnel Projects in Hebei Province of China,No.A201401041
文摘Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress pathways.Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury,and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra.Here,we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12,caspase-3 and the endoplasmic reticulum stress marker 78 k Da glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours.Furthermore,numbers of terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury.These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra,and may play an important role in the pathophysiology of secondary brain injury.
