BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To inve...BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To investigate the accuracy of AI diagnostic software(Shukun)in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion.METHODS From November 2021 to March 2022,consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy(MT)post-Shukun AI penumbra assessment were included.Computed tomography angiography(CTA)and perfusion exams were analyzed by AI,reviewed by senior neurointerventional experts.In the case of divergences among the three experts,discussions were held to reach a final conclusion.When the results of AI were inconsistent with the neurointerventional experts’diagnosis,the diagnosis by AI was considered inaccurate.RESULTS A total of 22 patients were included in the study.The vascular recanalization rate was 90.9%,and 63.6%of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up.The computed tomography(CT)perfusion diagnosis by Shukun(AI)was confirmed to be invalid in 3 patients(inaccuracy rate:13.6%).CONCLUSION AI(Shukun)has limits in assessing ischemic penumbra.Integrating clinical and imaging data(CT,CTA,and even magnetic resonance imaging)is crucial for MT decision-making.展开更多
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
OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R...OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.展开更多
Acute ischemic stroke has the characteristics of high disability,lethality and recurrence rate,which seriously threatens the health of middle-aged and elderly people.This article describes the acute ischemic stroke wi...Acute ischemic stroke has the characteristics of high disability,lethality and recurrence rate,which seriously threatens the health of middle-aged and elderly people.This article describes the acute ischemic stroke with internal carotid artery occlusion as the main clinical feature and discusses its treatment strategy.Treatment remedies:clinical diagnosis was carried out based on the present medical history,physical examination and craniocerebral CT(computed tomography).Neurological function was improved by intravenous thrombolysis,cerebrovascular angiography was used to clarify cerebrovascular occlusion,cerebral blood supply was identified by CT perfusion,and neurological function recovery was followed up.After intravenous thrombolysis,the patient’s consciousness turned clear and the right limb muscle strength recovery was not obvious,but the patient did not receive bridging therapy.Cerebral angiography showed about 90%stenosis at the beginning of the left internal carotid artery,and the blood flow terminated at the C7 segment.Cerebral CT perfusion imaging showed decreased perfusion in the left cerebral hemisphere,but the patient did not receive carotid endarterectomy and vascular bypass treatment.Post treatment evaluating:follow-up showed that NIHSS(National Institute of Health stroke scale)score was significantly decreased and limb function was significantly restored.Conclusion:early intravenous thrombolytic therapy can help reduce the area of ischemic penumbra and improve long-term prognosis.Severe vascular stenosis can stimulate vascular compensation,significantly reduce the range of ischemia when thrombus occurs,and effectively reduce the disability rate without bridging therapy.Whether vascular stenosis and occlusion are treated by vascular bypass,etc.,individualized plans should be made according to vascular compensation.展开更多
BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited it...BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited its application. OBJECTIVE: To observe the effects of recombinant Ngb plasmid in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Genetically engineered, randomized, controlled, animal experiment was performed at the Laboratory of Chongqing Medical University from May 2006 and January 2007. MATERIALS: 2, 3, 5-triphenyltetrazolium chloride was purchased from Shanghai Sangon Biological Engineering Technology and Services. Rabbit anti-rat Bcl-2 polyclonal antibody, rabbit anti-rat β-actin monoclonal antibody, and FITC-labeled goat anti-rabbit IgG were purchased from Sigma, USA. TUNEL apoptosis kit was purchased from Roche, Germany. METHODS: A total of 54 male, adult, Wistar rats were randomly assigned to 3 groups (n=18): normal saline, plasmid control, and recombinant Ngb (pCDNA3.1 (+)/Ngb). Normal saline, plasmid pCDNA3.1 (+), and recombinant plasmid pCDNA3.1 (+)/Ngb were separately injected into two sites in the rat cerebral cortex, and models of focal ischemia were established by occlusion of the right middle cerebral artery after 24 hours. MAIN OUTCOME MEASURES: Local ischemic damage was detected by 2, 3, 5- triphenyltetrazolium chloride staining, apoptosis in the penumbra was confirmed using the TUNEL method, and Bcl-2 protein expression in the penumbra was determined by indirect immunofluorescent staining and Western blot analysis. RESULTS: Compared with the normal saline and plasmid control groups, cerebral infarction size and the number of apoptotic cells in the pCDNA3.1 (+)/Ngb group were significantly reduced (P 〈 0.01). The percentage of Bcl-2-positive cells in the penumbra of the pCDNA3.1 (+)/Ngb group was significantly increased (P 〈 0.01). The relative expression level of Bcl-2 protein was increased by 40%-50%. CONCLUSION: Recombinant plasmid pCDNA3.1/Ngb provides neuroprotection by upregulating Bcl-2 expression and inhibiting cell apoptosis in the penumbra.展开更多
Glucose is the essential and almost exclusive metabolic fuel for the brain.Ischemic stroke caused by a blockage in one or more cerebral arteries quickly leads to a lack of regional cerebral blood supply resulting in s...Glucose is the essential and almost exclusive metabolic fuel for the brain.Ischemic stroke caused by a blockage in one or more cerebral arteries quickly leads to a lack of regional cerebral blood supply resulting in severe glucose deprivation with subsequent induction of cellular homeostasis disturbance and eventual neuronal death.To make up ischemiamediated adenosine 5′-triphosphate depletion,glucose in the ischemic penumbra area rapidly enters anaerobic metabolism to produce glycolytic adenosine 5′-triphosphate for cell survival.It appears that an increase in glucose in the ischemic brain would exert favorable effects.This notion is supported by in vitro studies,but generally denied by most in vivo studies.Clinical studies to manage increased blood glucose levels after stroke also failed to show any benefits or even brought out harmful effects while elevated admission blood glucose concentrations frequently correlated with poor outcomes.Surprisingly,strict glycaemic control in clinical practice also failed to yield any beneficial outcome.These controversial results from glucose management studies during the past three decades remain a challenging question of whether glucose intervention is needed for ischemic stroke care.This review provides a brief overview of the roles of cerebral glucose under normal and ischemic conditions and the results of managing glucose levels in non-diabetic patients.Moreover,the relationship between blood glucose and cerebral glucose during the ischemia/reperfusion processes and the potential benefits of low glucose supplements for non-diabetic patients are discussed.展开更多
Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of t...Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.展开更多
文摘BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To investigate the accuracy of AI diagnostic software(Shukun)in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion.METHODS From November 2021 to March 2022,consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy(MT)post-Shukun AI penumbra assessment were included.Computed tomography angiography(CTA)and perfusion exams were analyzed by AI,reviewed by senior neurointerventional experts.In the case of divergences among the three experts,discussions were held to reach a final conclusion.When the results of AI were inconsistent with the neurointerventional experts’diagnosis,the diagnosis by AI was considered inaccurate.RESULTS A total of 22 patients were included in the study.The vascular recanalization rate was 90.9%,and 63.6%of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up.The computed tomography(CT)perfusion diagnosis by Shukun(AI)was confirmed to be invalid in 3 patients(inaccuracy rate:13.6%).CONCLUSION AI(Shukun)has limits in assessing ischemic penumbra.Integrating clinical and imaging data(CT,CTA,and even magnetic resonance imaging)is crucial for MT decision-making.
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.
基金National Natural Science Foundation of China(81173596)Natural Science Foundation of the Department of Education of Anhui Province(KJ2015A157)
文摘OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.
文摘Acute ischemic stroke has the characteristics of high disability,lethality and recurrence rate,which seriously threatens the health of middle-aged and elderly people.This article describes the acute ischemic stroke with internal carotid artery occlusion as the main clinical feature and discusses its treatment strategy.Treatment remedies:clinical diagnosis was carried out based on the present medical history,physical examination and craniocerebral CT(computed tomography).Neurological function was improved by intravenous thrombolysis,cerebrovascular angiography was used to clarify cerebrovascular occlusion,cerebral blood supply was identified by CT perfusion,and neurological function recovery was followed up.After intravenous thrombolysis,the patient’s consciousness turned clear and the right limb muscle strength recovery was not obvious,but the patient did not receive bridging therapy.Cerebral angiography showed about 90%stenosis at the beginning of the left internal carotid artery,and the blood flow terminated at the C7 segment.Cerebral CT perfusion imaging showed decreased perfusion in the left cerebral hemisphere,but the patient did not receive carotid endarterectomy and vascular bypass treatment.Post treatment evaluating:follow-up showed that NIHSS(National Institute of Health stroke scale)score was significantly decreased and limb function was significantly restored.Conclusion:early intravenous thrombolytic therapy can help reduce the area of ischemic penumbra and improve long-term prognosis.Severe vascular stenosis can stimulate vascular compensation,significantly reduce the range of ischemia when thrombus occurs,and effectively reduce the disability rate without bridging therapy.Whether vascular stenosis and occlusion are treated by vascular bypass,etc.,individualized plans should be made according to vascular compensation.
基金a Grant from Chongqing Health Bureau, No. 06-2-177
文摘BACKGROUND: Adenovirus has been used to develop neuroglobin (Ngb) vectors. Although transfection efficiency is high, induced gene mutation, cytotoxicity, inflammation, and low exogenous gene content have limited its application. OBJECTIVE: To observe the effects of recombinant Ngb plasmid in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Genetically engineered, randomized, controlled, animal experiment was performed at the Laboratory of Chongqing Medical University from May 2006 and January 2007. MATERIALS: 2, 3, 5-triphenyltetrazolium chloride was purchased from Shanghai Sangon Biological Engineering Technology and Services. Rabbit anti-rat Bcl-2 polyclonal antibody, rabbit anti-rat β-actin monoclonal antibody, and FITC-labeled goat anti-rabbit IgG were purchased from Sigma, USA. TUNEL apoptosis kit was purchased from Roche, Germany. METHODS: A total of 54 male, adult, Wistar rats were randomly assigned to 3 groups (n=18): normal saline, plasmid control, and recombinant Ngb (pCDNA3.1 (+)/Ngb). Normal saline, plasmid pCDNA3.1 (+), and recombinant plasmid pCDNA3.1 (+)/Ngb were separately injected into two sites in the rat cerebral cortex, and models of focal ischemia were established by occlusion of the right middle cerebral artery after 24 hours. MAIN OUTCOME MEASURES: Local ischemic damage was detected by 2, 3, 5- triphenyltetrazolium chloride staining, apoptosis in the penumbra was confirmed using the TUNEL method, and Bcl-2 protein expression in the penumbra was determined by indirect immunofluorescent staining and Western blot analysis. RESULTS: Compared with the normal saline and plasmid control groups, cerebral infarction size and the number of apoptotic cells in the pCDNA3.1 (+)/Ngb group were significantly reduced (P 〈 0.01). The percentage of Bcl-2-positive cells in the penumbra of the pCDNA3.1 (+)/Ngb group was significantly increased (P 〈 0.01). The relative expression level of Bcl-2 protein was increased by 40%-50%. CONCLUSION: Recombinant plasmid pCDNA3.1/Ngb provides neuroprotection by upregulating Bcl-2 expression and inhibiting cell apoptosis in the penumbra.
基金supported by a grant from the National Institute of General Medical Sciences(SC1GM111178)to JX。
文摘Glucose is the essential and almost exclusive metabolic fuel for the brain.Ischemic stroke caused by a blockage in one or more cerebral arteries quickly leads to a lack of regional cerebral blood supply resulting in severe glucose deprivation with subsequent induction of cellular homeostasis disturbance and eventual neuronal death.To make up ischemiamediated adenosine 5′-triphosphate depletion,glucose in the ischemic penumbra area rapidly enters anaerobic metabolism to produce glycolytic adenosine 5′-triphosphate for cell survival.It appears that an increase in glucose in the ischemic brain would exert favorable effects.This notion is supported by in vitro studies,but generally denied by most in vivo studies.Clinical studies to manage increased blood glucose levels after stroke also failed to show any benefits or even brought out harmful effects while elevated admission blood glucose concentrations frequently correlated with poor outcomes.Surprisingly,strict glycaemic control in clinical practice also failed to yield any beneficial outcome.These controversial results from glucose management studies during the past three decades remain a challenging question of whether glucose intervention is needed for ischemic stroke care.This review provides a brief overview of the roles of cerebral glucose under normal and ischemic conditions and the results of managing glucose levels in non-diabetic patients.Moreover,the relationship between blood glucose and cerebral glucose during the ischemia/reperfusion processes and the potential benefits of low glucose supplements for non-diabetic patients are discussed.
基金financially supported by the National Natural Science Foundation of China,No.81301006a grant from Henan Provincial Scientific and Technological Research Projects of China,No.132102310092
文摘Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.