心脏磁共振在不明原因脑卒中病因筛查中的应用

目的探讨心脏磁共振成像技术在不明原因缺血性脑卒中患者病因筛查中的应用价值。方法选取2014年9月~2015年2月在我院诊治的不明原因缺血性脑卒中患者53例为研究对象,均行心脏MRI和经胸超声心动图检查,并对检查出卵圆孔未闭(PFO)的患者进行分析。结果 53例不明原因缺血性脑卒中患者中,心脏MRI检查诊断合并PFO为27例(50.94%),经胸超声动图(TTE)检查诊断合并PFO为7例(13.21%),差异有统计学意义(P0.001)。结论心脏MRI对PFO的检出率较高,可作为不明原因缺血性脑卒中患者病因筛查的有效手段。     

High Total Hospitalization Cost but Low Cost of Imaging Studies in Recurrent Acute Ischemic Stroke Patients

Background

Due to the high risk and severity of recurrence after stroke attack, recurrence is a major reason contributing to the disease burden. This study aims to determine whether recurrence is a significant contributor of hospitalization cost in items for ischemic stroke patients.

Methods

This study assessed acute ischemic stroke patients admitted to an academic medical center in 2003 through 2009. The t-test and Chi-square tests were used to compare first-ever and recurrent ischemic stroke groups in terms of total and categorized hospitalization cost, and multiple regression was performed to assess the influence of stroke recurrence.

Results

Recurrent ischemic strokes were associated with higher total cost, but examination cost showed no difference between the two groups. The recurrent stroke group showed higher laboratory but lower imaging cost. Of imaging studies, there was no significant difference in computed tomography scan cost while the first-ever stroke group spent more on magnetic resonance imaging and sonography. Controlling for other influential factors, recurrence was discovered to be a significant factor in lowering examination cost.

Conclusions

The findings of stroke recurrence in lowering examination cost could be explained from two perspectives, different clinical patterns of healthcare utilization and patients'' economic status in recurrent stroke.     

Increased Risk of Post-Thrombolysis Intracranial Hemorrhage in Acute Ischemic Stroke Patients with Leukoaraiosis: A Meta-Analysis

BackgroundLeukoaraiosis is common in patients with acute ischemic stroke. The results from many studies investigating the association between leukoaraiosis and intracranial hemorrhage after thrombolysis remain conflicting.MethodsA meta-analysis was performed to compare the risk of post-thrombolytic intracranial hemorrhage in patients with and without leukoaraiosis. Relevant reports were identified by searching PubMed, EmBase, Cochrane Library, and ISI Web of Science through December 2015 using a combination of subjective and random terms. Eligible studies that were original articles with a clear definition of leukoaraiosis and intracranial hemorrhage were selected and analyzed. Funnel plots, Egger’s test, and Begg’s test were conducted to assess the publication bias. Sensitivity analysis was also performed to evaluate the influence of each individual study.ResultsEleven trials that enrolled 6912 participants were included. There was a significantly increased risk for acute ischemic stroke patients with leukoaraiosis (odds ratio: 1.89, 95% confidence interval 1.51–2.37, P<0.001). Low heterogeneity and less publication bias was detected among these studies. The results of both computed tomography and magnetic resonance imaging performed on the subgroups of leukoaraiosis were significant. Furthermore, an association between leukoaraiosis and symptomatic intracranial hemorrhage was also confirmed. The odds ratios remained stable with no obvious variations on the sensitivity analysis. The limitations consisted of types of including trials and not matching some baseline variables.ConclusionsThe results of this meta-analysis show that leukoaraiosis approximately doubles the incidence of intracranial hemorrhage after thrombolytic therapy. However, it does not critically affect decision making regarding thrombolysis for patients with acute ischemic stroke. Additional investigations are required.     

In vivo diffusion-perfusion magnetic resonance imaging of acute cerebral ischemia.

We compared the anatomic extent and severity of ischemic brain injury shown on diffusion-weighted magnetic resonance (MR) images, with cerebral tissue perfusion deficits demonstrated by a nonionic intravascular T2*-shortening magnetic susceptibility contrast agent used in conjunction with standard T2-weighted spin-echo and gradient-echo echo-planar images. Diffusion-weighted images displayed increased signal intensity in the vascular territory of the middle cerebral artery 25-40 min after permanent occlusion, whereas T2-weighted images without contrast were negative or equivocal for at least 2-3 h after stroke was induced. Contrast-enhanced T2-weighted and echo-planar images revealed perfusion deficits that were spatially closely related to the anatomic regions of ischemic tissue injury. These data indicate that diffusion-weighted MR images are very sensitive to early onset pathophysiologic changes induced by acute cerebral ischemia. Combined sequential diffusion-perfusion imaging enables noninvasive in vivo examination of the relationship between hypoperfusion and evolving ischemic brain injury.     

Neuroprotective Mechanism of BNG-1 against Focal Cerebral Ischemia: A Neuroimaging and Neurotrophin Study

BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.     

MRI Features in a Canine Model of Ischemic Stroke: Correlation between Lesion Volume and Neurobehavioral Status during the Subacute Stage

The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI) and assess the correlation between the volume of the ischemic lesion and neurobehavioral status during the subacute stage of ischemic stroke. Ischemic stroke was induced in 6 healthy laboratory beagles through permanent occlusion of the middle cerebral artery (MCAO). T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), measurement of the apparent diffusion coefficient (ADC) ratio, and neurobehavioral evaluation were performed 3 times serially by using a 1.5-T MR system: before and 3 and 10 d after MCAO. Ischemic lesions demonstrated T2 hyperintensity, FLAIR hyperintensity, and DWI hyperintensity. The ADC ratio was decreased initially but then was increased at 10 d after MCAO. Ischemic lesion volumes on T2-weighted and FLAIR imaging were not significantly different from those on DWI. The lesion volume and neurobehavioral score showed strong correlation. Our results suggest that conventional MRI may be a reliable diagnostic tool during the subacute stage of canine ischemic stroke.Abbreviations: ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; MCAO, middle cerebral artery occlusion; MRI, magnetic resonance imaging; PWI, perfusion-weighted imagingIn human medicine, stroke is a leading cause of adult mortality and neurologic disability worldwide.¹ Strokes previously were thought to be uncommon in small animals, but the true prevalence is unknown.⁴ These events are now recognized more frequently in dogs because of increased use of magnetic resonance imaging (MRI).^5,14,17Because the infusion of thrombolytic agents, such as urokinase or tissue plasminogen activator, within 3 to 6 h of the onset symptoms is effective in restoring blood flow and improving stroke outcome in humans,¹⁹ the detection of early ischemic changes is now thought to be necessary to improve patient outcome. Computed tomography and conventional MRI are not sufficiently sensitive to predict the presence and extent of ischemic damage during the acute stage after a stroke.^12,20 Therefore several MRI sequences, such as fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and MR angiography, have been developed for early diagnosis and subsequent follow-up of ischemic stroke.³ High-field magnetic strengths (at least 1.5 T) are necessary to perform these sequences.In contrast to the situation in humans, ischemic stroke in many dogs is diagnosed during the subacute stage—24 h to 6 wk after the vascular insult—due to the time lag between the onset of clinical signs to referral and to the lack of standard diagnostic protocols for ischemic stroke in dogs. In most reports of strokes in dogs, the median interval between the onset of neurologic dysfunction and performance of an MRI was more than 2 d.^5,14,17 Whereas DWI has marked sensitivity to very early ischemic changes in the brain, T2-weighted and FLAIR images gradually become more hyperintense later (that is, during the first 24 h after the insult).³ Therefore, hyperintensity on T2-weighted and FLAIR images is believed to be representative of mature lesions.¹⁵ In light of these findings, we hypothesized that conventional MR sequences, such as T2-weighted and FLAIR imaging as well as DWI would be used for the diagnosis of the subacute stage of ischemic stroke in dogs.The purpose of this study was to evaluate the diagnostic value of MRI and assess the correlation between the volume of ischemic lesions and neurobehavioral status during the subacute stage of ischemic stroke in dogs. We therefore investigated the lesion volume of T2-weighted and FLAIR images compared with that on DWI images. Furthermore, we assessed the relationship between the apparent diffusion coefficient (ADC) of the ischemic lesions and the neurobehavioral status of the dogs.     

ApoC-I and ApoC-III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke

Early diagnosis and immediate therapeutic interventions are crucial factors to reduce the damage extent and the risk of death. Currently, the diagnosis of stroke relies on neurological assessment of the patient and neuro-imaging techniques including computed tomography and/or magnetic resonance imaging scan. An early diagnostic marker of stroke, ideally capable to discriminate ischemic from hemorrhagic stroke would considerably improve patient acute management. Using surface-enhanced laser desorption/ionization (SELDI) technology, we aimed at finding new early diagnostic plasmatic markers of stroke. Strong anionic exchange (SAX) SELDI profiles of plasma samples from 21 stroke patients were compared to 21 samples from healthy controls. Seven peaks appeared to be differentially expressed with significant p values (p < 0.05). Proteins were stripped from the SAX chips, separated on a one-dimensional electrophoresis (1-DE) gel and stained using mass spectrometry (MS)-compatible silver staining. Following in-gel tryptic digestion, the peptides were analyzed by MS. Four candidate proteins were identified as apolipoprotein CI (ApoC-I), apolipoprotein CIII (ApoC-III), serum amyloid A (SAA), and antithrombin-III fragment (AT-III fragment). Assessment of ApoC-I and ApoC-III levels in plasma samples using a sandwich enzyme-linked immunosorbent assay (ELISA) allowed to distinguish between hemorrhagic (n = 15) and ischemic (n = 16) stroke (p < 0.001). To the best of our knowledge, ApoC-I and ApoC-III are the first reported plasmatic biomarkers capable to accurately distinguish between ischemic and hemorrhagic stroke in a small number of patients. It requires further investigation in a large cohort of patients.     

Biomarkers and perfusion – training-induced changes after stroke (BAPTISe): protocol of an observational study accompanying a randomized controlled trial

Background

Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke.

Methods/design

This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions.

Discussion

This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke.

Trial registration

NCT01954797.

     

Altered Resting-State fMRI Signals in Acute Stroke Patients with Ischemic Penumbra

Background

Identifying the ischemic penumbra in acute stroke subjects is important for the clinical decision making process. The aim of this study was to use resting-state functional magnetic resonance singal (fMRI) to investigate the change in the amplitude of low-frequency fluctuations (ALFF) of these subjects in three different subsections of acute stroke regions: the infarct core tissue, the penumbra tissue, and the normal brain tissue. Another aim of this study was to test the feasilbility of consistently detecting the penumbra region of the brain through ALFF analysis.

Methods

Sixteen subjects with first-ever acute ischemic stroke were scanned within 27 hours of the onset of stroke using magnetic resonance imaging. The core of infarct regions and penumbra regions were determined by diffusion and perfusion-weighted imaging respectively. The ALFF were measured from resting-state blood oxygen level dependent (BOLD) fMRI scans. The averaged relative ALFF value of each regions were correlated with the time after the onset of stroke.

Results

Relative ALFF values were significantly different in the infarct core tissue, penumbra tissue and normal brain tissue. The locations of lesions in the ALFF maps did not match perfectly with diffusion and perfusion-weighted imagings; however, these maps provide a contrast that can be used to differentiate between penumbra brain tissue and normal brain tissue. Significant correlations between time after stroke onset and the relative ALFF values were present in the penumbra tissue but not in the infarct core and normal brain tissue.

Conclusion

Preliminary results from this study suggest that the ALFF reflects the underlying neurovascular activity and has a great potential to estimate the brain tissue viability after ischemia. Results also show that the ALFF may contribute to acute stroke imaging for thrombolytic or neuroprotective therapies.     

INFLAM – INFLAMmation in Brain and Vessels with Iron Nanoparticles and Cell Trafficking: A Multiscale Approach of Tissue Microenvironment,Iron Nanostructure and Iron Biotransformation

Background

Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke.

White Matter Reorganization and Functional Response after Focal Cerebral Ischemia in the Rat

After stroke, the brain has shown to be able to achieve spontaneous functional recovery despite severe cerebral damage. This phenomenon is poorly understood. To address this issue, focal transient ischemia was induced by 60 min middle cerebral artery occlusion in Wistar rats. The evolution of stroke was followed using two magnetic resonance imaging modalities: diffusion spectrum imaging (acquired before, one and four weeks after stroke) and functional magnetic resonance imaging (acquired before and five weeks after stroke). To confirm the imaging observations, immunohistochemical staining for myelin, astrocytes and macrophages/microglia was added. At four weeks after stroke, a focal alteration of the diffusion anisotropy was observed between the ipsilesional ventricle and the lesion area. Using tractography this perturbation was identified as reorganization of the ipsilesional internal capsule. Functional imaging at five weeks after ischemia demonstrated activation of the primary sensorimotor cortex in both hemispheres in all rats except one animal lacking a functional response in the ipsilesional cortex. Furthermore, fiber tracking showed a transhemispheric fiber connection through the corpus callosum, which-in the rat without functional recovery-was lost. Our study shows the influence of the internal capsule reorganization, combined with inter-hemispheric connections though the corpus callosum, on the functional activation of the brain from stroke. In conclusion, tractography opens a new door to non-invasively investigate the structural correlates of lack of functional recovery after stroke.     

Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke

Vascular endothelial growth factor (VEGF), an angiogenic factor produced in response to ischemic injury, promotes vascular permeability (VP). Evidence is provided that Src kinase regulates VEGF-mediated VP in the brain following stroke and that suppression of Src activity decreases VP thereby minimizing brain injury. Mice lacking pp60c-src are resistant to VEGF-induced VP and show decreased infarct volumes after stroke whereas mice deficient in pp59c-fyn, another Src family member, have normal VEGF-mediated VP and infarct size. Systemic application of a Src-inhibitor given up to six hours following stroke suppressed VP protecting wild-type mice from ischemia-induced brain damage without influencing VEGF expression. This was associated with reduced edema, improved cerebral perfusion and decreased infarct volume 24 hours after injury as measured by magnetic resonance imaging and histological analysis. Thus, Src represents a key intermediate and novel therapeutic target in the pathophysiology of cerebral ischemia where it appears to regulate neuronal damage by influencing VEGF-mediated VP.     

Iron overload,measured as serum ferritin,increases brain damage induced by focal ischemia and early reperfusion

High levels of iron, measured as serum ferritin, are associated to a worse outcome after stroke. However, it is not known whether ischemic damage might increase ferritin levels as an acute phase protein or whether iron overload affects stroke outcome. The objectives are to study the effect of stroke on serum ferritin and the contribution of iron overload to ischemic damage.     

Cognitive State following Stroke: The Predominant Role of Preexisting White Matter Lesions

Background and purpose

Stroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions'' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state.

Methods

Consecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions'' volume.

Results

Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β = −0.231) and normal appearing white matter integrity (β = −0.176) on the global cognitive score, while ischemic lesions'' volume showed no such effect (β = 0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092).

Conclusions

Mild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration.     

弥散加权成像及1H磁共振波谱在新生儿缺氧缺血性脑病中的诊断价值

目的:探讨弥散加权成像、1H磁共振波谱诊断新生儿缺氧缺血性脑病的应用价值。方法:以本院收治的缺氧缺血性脑病新生儿37例为研究组,另选择健康新生儿40例作为对照组,两组新生儿均接受弥散加权成像及1H磁共振波谱检查,观察研究组新生儿普通MRI与弥散加权成像检查结果,对比研究组和对照组新生儿的脑代谢化合物相对浓度。结果:与普通MRI检出率相比,研究组患儿的弥散加权成像信号明显升高,差异存在统计学意义(P0.05)。研究组NAA/Cr比值低于对照组,Cho/Cr、MI/Cr、Glu-Gln/Cr、Lac/Cr比值高于对照组,差异存在统计学意义(P0.05)。结论:临床上诊断新生儿缺氧缺血性脑病时,弥散加权成像与1H磁共振波谱的联合应用可提升诊断准确率,通过对代谢物浓度的分析有利于评价缺氧缺血导致脑组织损害的严重程度。     

Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI

In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.     

Stroke pathophysiology: management challenges and new treatment advances

Stroke is the second leading cause of death and the first cause of lost disability-adjusted years in developed countries. During the past decade, new developments in thrombolytic therapy have led to the implementation of emergency intervention protocols for the treatment of ischemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Treatment with rtPA has shown to be effective within the first 3 hours following stroke onset and the FDA and the European Medical Agency (EMEA) have approved its use. Acknowledging the urgency and intricacies of stroke, Stroke Units allow the monitoring of physiological parameters in the acute phase of stroke and are considered an important management tool that can significantly improve the quality of care provided to the patient. The concept of neuroprotective therapy for acute ischemic stroke to salvage tissue at risk and improve functional outcome is based on sound scientific principles and extensive preclinical animal studies demonstrating efficacy. However, most neuroprotective drugs in clinical trials have failed, possibly due to inadequate preclinical testing or flawed clinical development programs. Several new treatment strategies are under development and are being tested. This review is directed at understanding the management of acute ischemic stroke pathophysiology. We address the management challenges and new treatment advances by integrating the knowledge of possible pharmacological targets for acute ischemic stroke. We hope to shed new light upon the controversy surrounding the management of acute ischemic stroke in an attempt to elucidate why failed clinical trials continue to occur despite promising neuroprotective preclinical studies.     

Quantitative Susceptibility Mapping-Based Microscopy of Magnetic Resonance Venography (QSM-mMRV) for In Vivo Morphologically and Functionally Assessing Cerebromicrovasculature in Rat Stroke Model

Abnormal cerebral oxygenation and vessel structure is a crucial feature of stroke. An imaging method with structural and functional information is necessary for diagnosis of stroke. This study applies QSM-mMRV (quantitative susceptibility mapping-based microscopic magnetic resonance venography) for noninvasively detecting small cerebral venous vessels in rat stroke model. First, susceptibility mapping is optimized and calculated from magnetic resonance (MR) phase images of a rat brain. Subsequently, QSM-mMRV is used to simultaneously provide information on microvascular architecture and venous oxygen saturation (SvO₂), both of which can be used to evaluate the physiological and functional characteristics of microvascular changes for longitudinally monitoring and therapeutically evaluating a disease model. Morphologically, the quantification of vessel sizes using QSM-mMRV was 30% smaller than that of susceptibility-weighted imaging (SWI), which eliminated the overestimation of conventional SWI. Functionally, QSM-mMRV estimated an average SvO₂ ranging from 73% to 85% for healthy rats. Finally, we also applied QSM to monitor the revascularization of post-stroke vessels from 3 to 10 days after reperfusion. QSM estimations of SvO₂ were comparable to those calculated using the pulse oximeter standard metric. We conclude that QSM-mMRV is useful for longitudinally monitoring blood oxygen and might become clinically useful for assessing cerebrovascular diseases.     

Traditional Chinese medicines with caspase-inhibitory activity

Clinical evidence indicates that traditional Chinese medicine (TCM) drugs can reduce stroke-inflicted brain damage. To date, the molecular basis of the apparent neuroprotective effects of these TCM drugs remains largely obscure. Several lines of evidence indicate that the activation of cell death programs leads to the loss of neurons during the reperfusion phase of ischemic stroke. In particular, activation of caspases (cysteinyl aspartate-specific proteinases) is a critical step in neuronal apoptosis. Using nuclear magnetic resonance (NMR) and fluorescence assays, we screened a collection of 58 TCM drugs that are commonly used in stroke therapy for caspase inhibitory activity. We found that aqueous extracts of Lianqiao (Fructus Forsythiae) and Shouwuteng (Caulis Polygoni multiflori) blocked the activity of the initiator caspase-8 as well as the effector caspase-3 and caspase-7 in a dose-dependent manner with an IC(50)10 microg/ml. Identification of caspase inhibitory activity of these TCM drugs, allows the formulation of testable hypotheses and design of further investigations aimed at the elucidation of the molecular basis of TCM stroke therapy.     

The efficacy and safety of cilostazol for the secondary prevention of ischemic stroke in acute and chronic phases in Asian population- an updated meta-analysis

Backgrounds

While previous meta-analysis have investigated the efficacy of cilostazol in the secondary prevention of ischemic stroke, they were criticized for their methodology, which confused the acute and chronic phases of stroke. We present a new systematic review, which differs from previous meta-analysis by distinguishing between the different phases of stroke, and includes two new randomized, controlled trials (RCTs).

Methods

All RCTs investigating the effect of cilostazol on secondary prevention of ischemic stroke were obtained. Outcomes were analyzed by Review Manager, including recurrence of cerebral infarction (ROCI), hemorrhage stroke or subarachnoid hemorrhage (HSSH), all-cause death (ACD), and modified Rankin Scale score (mRS). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the quality of the evidence.

Results

5491 patients from six studies were included in the current study. In secondary prevention of ischemic stroke in chronic phase, cilostazol was associated with a 47% reduction in ROCI (relative risk [RR] 0.53, 95% confidence interval [CI] 0.34 to 0.81, p?=?0.003), while no significant difference in HSSH and ACD compared with placebo; and 71% reduction in HSSH (RR 0.29, 95% CI 0.15 to 0.56, p?=?0.0002) compared with aspirin, but not in ROCI and ACD. In the secondary prevention of ischemic stroke in acute phase, cilostazol did not show any effect in the ROCI, HSSH, ACD and mRS compared to placebo or aspirin. The quality of the evidence from chronic phase was high or moderate, and those from acute phase were moderate or low when analyzed by GRADE approach.

Conclusion

Cilostazol provided a protective effect in the secondary prevention of the chronic phase of ischemic stroke.