A physiological state of＂normoxia＂obtains when tissue oxygen tension（pO_2）is sufficient to drive mitochondrial respiration throughout a volume of cells.Between 30-40%of the available oxygen is normally extracted f...A physiological state of＂normoxia＂obtains when tissue oxygen tension（pO_2）is sufficient to drive mitochondrial respiration throughout a volume of cells.Between 30-40%of the available oxygen is normally extracted from hemoglobin as it passes through neural tissue.展开更多
BACKGROUND Blood-brain barrier(BBB)disruption plays an important role in the development of neurological dysfunction in ischemic stroke.However,diagnostic modalities that can clearly diagnose the degree of BBB disrupt...BACKGROUND Blood-brain barrier(BBB)disruption plays an important role in the development of neurological dysfunction in ischemic stroke.However,diagnostic modalities that can clearly diagnose the degree of BBB disruption in ischemic stroke are limited.Here,we describe two cases in which the usefulness of dynamic contrastenhanced magnetic resonance imaging(DCE-MRI)in detecting BBB disruption was evaluated after treatment of acute ischemic stroke using two different methods.CASE SUMMARY The two patients of similar age and relatively similar cerebral infarction locations were treated conservatively or with thrombectomy,although their sex was different.As a result of analysis by performing DCE-MRI,it was confirmed that BBB disruption was significantly less severe in the patient who underwent thrombectomy(P=3.3×10^(-7)),whereas the average Ktrans of the contralateral hemisphere in both patients was similar(2.4×10^(-5)min^(-1) and 2.0×10^(-5)min^(-1)).If reperfusion is achieved through thrombectomy,it may indicate that the penumbra can be saved and BBB recovery can be promoted.CONCLUSION Our cases suggest that BBB disruption could be important if BBB permeability is used to guide clinical treatment.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 strok...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
The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 m...The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5 triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle treated group, pretreatment with 3 NPA could reduce the infarct volume by 23.3 % and decrease the number of TUNEL positive neural cells and apoptotic percentage by 47 % ( P< 0.05) and 44.9 % ( P< 0 01), respectively. It was concluded that the development of 3 NPA induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis.展开更多
Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location...Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment,with less attention to predictions of outcomes after thrombolysis.Thus,in the present study,we assessed the efficacy of combined computed tomography（CT） perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients.The study included 52 patients who received both CT perfusion and CT angiography.Patients were grouped based on the following criteria to compare clinical outcomes：（1） thrombolytic and non-thrombolytic patients,（2） thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis,（3） thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch,and（4） different CT angiography and CT perfusion results.Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change.Long-term outcome was assessed by the 3-month modified Rankin Scale score.Of 52 ischemic stroke patients,29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment（23 patients）.Patients with both vascular stenosis and blood flow mismatch（13 patients） exhibited the best short-term outcome,while there was no correlation of long-term outcome with CT angiography or CT perfusion findings.These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome,but not long-term outcome,after thrombolysis.展开更多
OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.Howe...OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.However,the effect of URB597 on cerebral isch⁃emic injury in mice remains unclear.METHODS Focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min followed by reperfusion for 24 h in mice.To observe the dose-dependent effect,URB597(0.04-5.00 mg·kg-1,ip)was administered at the same time of reperfu⁃sion.To determine the time-dependent effect,URB597(1.00 mg·kg-1,ip)was administered as a single dose at 0,1,3 or 5 h after reperfusion.Twenty-four hours after brain ischemia,Beder⁃son scoring test and grip strength test were used to evaluate the neurological function;brain in⁃farct volume was assayed by 2,3,5-triphenyltetra⁃zolium chloride(TTC)staining or diffusion-weighted magnetic resonance imaging(MRI).Laser speckle imaging(LSI)technique was used to assay the regional cerebral blood flow(rCBF);NeuN immunofluorescence staining was used to observe the neuron survival in the penumbra.To further investigate the underlying mechanism,au⁃tophagy flux related proteins(LC3-Ⅱ,P62 and LAMP2)and necroptosis related proteins(pRIPK3 and pMLKL)were detected by Western blotting and immunofluorescence staining.RESULTS Twenty-four hours after brain ischemia,URB597 dose-dependently improved neurological func⁃tion and reduced brain infarct volume.The most effective dose was 1.00 mg·kg-1;the therapeutic time window was within 1 h after ischemic stroke.The protective effect is further confirmed by the results that post-ischemic treatment with URB597(1.00 mg·kg-1)significantly increased neurons survival,promoted autophagy flux and reduced cell necroptosis in cortical penumbra after cerebral I/R.CONCLUSION URB597 dose-and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury.This neu⁃roprotective effect of URB597 may be associated with its restoration of autophagy flux and inhibi⁃tion of neuronal necroptosis in the cortical penumbra.展开更多
文摘A physiological state of＂normoxia＂obtains when tissue oxygen tension（pO_2）is sufficient to drive mitochondrial respiration throughout a volume of cells.Between 30-40%of the available oxygen is normally extracted from hemoglobin as it passes through neural tissue.
基金Supported by the National Research Foundation of Korea grant,No.2019M3E5D1A02069399
文摘BACKGROUND Blood-brain barrier(BBB)disruption plays an important role in the development of neurological dysfunction in ischemic stroke.However,diagnostic modalities that can clearly diagnose the degree of BBB disruption in ischemic stroke are limited.Here,we describe two cases in which the usefulness of dynamic contrastenhanced magnetic resonance imaging(DCE-MRI)in detecting BBB disruption was evaluated after treatment of acute ischemic stroke using two different methods.CASE SUMMARY The two patients of similar age and relatively similar cerebral infarction locations were treated conservatively or with thrombectomy,although their sex was different.As a result of analysis by performing DCE-MRI,it was confirmed that BBB disruption was significantly less severe in the patient who underwent thrombectomy(P=3.3×10^(-7)),whereas the average Ktrans of the contralateral hemisphere in both patients was similar(2.4×10^(-5)min^(-1) and 2.0×10^(-5)min^(-1)).If reperfusion is achieved through thrombectomy,it may indicate that the penumbra can be saved and BBB recovery can be promoted.CONCLUSION Our cases suggest that BBB disruption could be important if BBB permeability is used to guide clinical treatment.
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ThisprojectwassupportedbyagrantfrominitiativeFoundationofNatioualEducationMinistryforscholarscomingbackfromothercountries (No .2 0 0 1 345)
文摘The involvement of apoptosis in mitochondrial toxin 3 nitropropionic acid (3 NPA) induced ischemic tolerance to transient focal cerebral ischemia in rats and the mechanism was investigated. 3 NPA at a dose of 20 mg/kg or vehicle control was intraperitoneally into the rats. Three days later, rats were exposed to 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Infarct volumes were assessed by 2,3,5 triphenyltetrazolinm chloride (TTC) staining 24 h after reperfusion. Neural cell apoptosis in cerebral ischemic penumbra was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin in situ nick end labeling (TUNEL) and flow cytometry methods (FCM). The results showed that as compared to the vehicle treated group, pretreatment with 3 NPA could reduce the infarct volume by 23.3 % and decrease the number of TUNEL positive neural cells and apoptotic percentage by 47 % ( P< 0.05) and 44.9 % ( P< 0 01), respectively. It was concluded that the development of 3 NPA induced ischemic tolerance in brain might be related to the decreases in neural cell apoptosis.
基金supported by the Science and Technical Committee of Shanghai Municipality of China,No.16QA1400900the Outstanding Youth Grant from Shanghai Municipal Commission of Health and Family Planning of China,No.XYQ2013107+1 种基金the China Postdoctoral Science Foundation,No.2016M592595the National Key Research and Development Program of China,No.2016YFA0203700
文摘Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment,with less attention to predictions of outcomes after thrombolysis.Thus,in the present study,we assessed the efficacy of combined computed tomography（CT） perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients.The study included 52 patients who received both CT perfusion and CT angiography.Patients were grouped based on the following criteria to compare clinical outcomes：（1） thrombolytic and non-thrombolytic patients,（2） thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis,（3） thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch,and（4） different CT angiography and CT perfusion results.Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change.Long-term outcome was assessed by the 3-month modified Rankin Scale score.Of 52 ischemic stroke patients,29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment（23 patients）.Patients with both vascular stenosis and blood flow mismatch（13 patients） exhibited the best short-term outcome,while there was no correlation of long-term outcome with CT angiography or CT perfusion findings.These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome,but not long-term outcome,after thrombolysis.
基金National Natural Science Foundation of China(81603093)and the Open Research Fund of State Key Laboratory of Cellu⁃lar Stress Biology,Xiamen University(SKLC⁃SB2019KF016)。
文摘OBJECTIVE URB597(KDS-4103)is a potent and selective inhibitor of the enzyme fatty acid amide hydrolase(FAAH)and can ele⁃vate the level of oleoylethanolamide(OEA),a naturally occurring endocannabinoid in the brain.However,the effect of URB597 on cerebral isch⁃emic injury in mice remains unclear.METHODS Focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min followed by reperfusion for 24 h in mice.To observe the dose-dependent effect,URB597(0.04-5.00 mg·kg-1,ip)was administered at the same time of reperfu⁃sion.To determine the time-dependent effect,URB597(1.00 mg·kg-1,ip)was administered as a single dose at 0,1,3 or 5 h after reperfusion.Twenty-four hours after brain ischemia,Beder⁃son scoring test and grip strength test were used to evaluate the neurological function;brain in⁃farct volume was assayed by 2,3,5-triphenyltetra⁃zolium chloride(TTC)staining or diffusion-weighted magnetic resonance imaging(MRI).Laser speckle imaging(LSI)technique was used to assay the regional cerebral blood flow(rCBF);NeuN immunofluorescence staining was used to observe the neuron survival in the penumbra.To further investigate the underlying mechanism,au⁃tophagy flux related proteins(LC3-Ⅱ,P62 and LAMP2)and necroptosis related proteins(pRIPK3 and pMLKL)were detected by Western blotting and immunofluorescence staining.RESULTS Twenty-four hours after brain ischemia,URB597 dose-dependently improved neurological func⁃tion and reduced brain infarct volume.The most effective dose was 1.00 mg·kg-1;the therapeutic time window was within 1 h after ischemic stroke.The protective effect is further confirmed by the results that post-ischemic treatment with URB597(1.00 mg·kg-1)significantly increased neurons survival,promoted autophagy flux and reduced cell necroptosis in cortical penumbra after cerebral I/R.CONCLUSION URB597 dose-and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury.This neu⁃roprotective effect of URB597 may be associated with its restoration of autophagy flux and inhibi⁃tion of neuronal necroptosis in the cortical penumbra.
