Research on the relationship between fibrinogen level and subtypes of the TOAST criteria in the acute ischemic stroke

Background

Cerebral infarction caused by different reasons seems differ in fibrinogen levels, so the current work intends to explore the relationship between the fibrinogen level and subtypes of the TOAST criteria in the acute stage of ischemic stroke.

Methods

A total of 577 case research objects were treated acute ischemic stroke patients in our hospital from December 2008 to December 2010, and blood samples within 72 hours of the onset were processed with the fibrinogen (PT-der) measurement. Classification of selected patients according to the TOAST Criteria was conducted to study the distribution of fibrinogen levels in the stroke subtypes.

Results

The distribution of fibrinogen levels in the subtypes was observed to be statistically insignificant.

Conclusions

In the acute stage of ischemic stroke, fibrinogen level was not related to the subtypes of the TOAST criteria.

     

Carotid plaque rather than intima-media thickness as a predictor of recurrent vascular events in patients with acute ischemic stroke

Background

To investigate the impacts of carotid plaque and intima-media thickness (IMT) on future vascular events (VEs) in the patients with acute ischemic stroke.

Methods

A total of 479 consecutive Korean patients with acute ischemic stroke were divided into 2 groups according to development of VEs; VE group (65.4 ± 10.9 years) vs no VE group (62.8 ± 13.2 years). VEs were defined as the development of recurrent stroke, coronary events, peripheral arterial disease, and death. Clinical, laboratory, and imaging findings were compared between the groups.

Results

During 105.5 ± 29.0 months of follow up, VEs were developed in 142 patients (29.6%). In univariate analysis, VEs were significantly associated with age, gender, diabetes, renal function, lipid levels, left ventricular function, carotid plaque or IMT. In multivariate analysis, the presence of carotid plaque, diabetes, renal function and male gender were independent predictors of future VEs in the patients with ischemic stroke, but carotid IMT was not a predictor of future VEs. Event free survival was significantly lower in patients with carotid plaque than without carotid plaque on Kaplan-Meier analysis (log rank p < 0.001).

Conclusion

The present study demonstrated that diabetes, impaired renal function, male gender, and the presence of carotid plaque rather than IMT were independent predictors of future VEs in Korean patients with acute ischemic stroke. Active medical management and careful monitoring for the development of recurrent VEs are strongly recommended in patients with acute ischemic stroke and carotid plaque.

     

Predictors of post-stroke body temperature elevation

Background

Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke.

Methods

The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature.

Results

Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC ?0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein?>?50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke.

Conclusions

In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.

     

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China

Background

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF.

Methods

Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis.

Results

Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR?=?4.70, 95%CI, 1.64–13.5), advanced age (OR?=?1.06, 95%CI, 1.04–1.09), NIHSS at admission (OR?=?1.06, 95%CI, 1.02–1.10), blood high density lipoprotein (HDL) (OR?=?1.52, 95%CI, 1.09–2.13), together with blood triglycerides (OR?=?0.64, 95%CI, 0.45–0.91) were independently associated with newly-detected AF.

Conclusions

Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF.

Trial registration

NCT02156765 (June 5, 2014).

     

rLOAD: does sex mediate the effect of acute antiplatelet loading on stroke outcome

Background

Biologic sex can influence response to pharmacologic therapy. The purpose of this proof-of-concept study was to evaluate the medicating effects of estrogen in the efficacy of acute antiplatelet loading therapy on stroke outcome in the rabbit small clot embolic model.

Methods

Female and male (20/group) New Zealand White rabbits were embolized to produce embolic stroke by injecting small blood clots into the middle cerebral artery via an internal carotid artery catheter. Two hours after embolization, rabbits were treated with standard dose antiplatelet loading (aspirin 10 mg/kg plus clopidogrel 10 mg/kg). Primary outcome measures were platelet inhibition, behavioral outcome P₅₀ (the weight of microclots (mg) that produces neurologic dysfunction in 50% of a group of animals), and effect of endogenous estrogen on outcome.

Results

For the first time in a non-rodent model of stroke, it was found that higher endogenous estrogen levels resulted in significantly better behavioral outcome in female subjects (r_s ?0.70, p?<?0.011). Platelet inhibition in response to collagen, arachidonic acid, and adenosine diphosphate (ADP) was not significantly different in females with higher vs. lower estrogen levels.

Conclusions

Behavioral outcomes are improved with females with higher endogenous estrogen levels treated with standard dose antiplatelet loading. This is the first non-rodent study to demonstrate that higher endogenous estrogen levels in female rabbits appear to be neuroprotective in ischemic stroke. This research supports the further study of the effect of endogenous estrogen levels on outcome with standard dose antiplatelet loading in stroke patients not eligible for revascularization therapies.

     

Artery buckling affects the mechanical stress in atherosclerotic plaques

Background

Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque.

Methods

Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature.

Results

Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque.

Conclusions

Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.

     

Cerebral infarcts associated with adenomyosis: a rare risk factor for stroke in middle-aged women: a case series

Background

Adenomyosis is a benign disease with elevated CA125 level.

Case presentation

We report 3 cases with adenomyosis who developed ischemic stroke during menstruation. The levels of CA125, CA19–9, and D-dimer were elevated, which dropped markedly after the menstrual phase. The development of nonbacterial thrombotic endocarditis (NBTE) and stenosis of the cerebral arteries associated with hypercoagulable state and the hyperviscosity nature of the mucinous protein may be the underlying mechanisms.

Conclusion

Our report suggests that adenomyosis might be a risk factor for ischemic stroke in middle-aged patients.

     

A prospective cohort study of stroke characteristics,care, and mortality in a hospital stroke registry in Vietnam

Background

As low and middle-income countries such as Vietnam experience the health transition from infectious to chronic diseases, the morbidity and mortality from stroke will rise. In line with the recommendation of the Institute of Medicine’s report on “Promoting Cardiovascular Health in the Developing World” to “improve local data”, we sought to investigate patient characteristics and clinical predictors of mortality among stroke inpatients at Da Nang Hospital in Vietnam.

Methods

A stroke registry was developed and implemented at Da Nang Hospital utilizing the World Health Organization’s Stroke STEPS instrument for data collection.

Results

754 patients were hospitalized for stroke from March 2010 through February 2011 and admitted to either the intensive care unit or cardiology ward. Mean age was 65 years, and 39% were female. Nearly 50% of strokes were hemorrhagic. At 28-day follow-up, 51.0% of patients with hemorrhagic stroke died whereas 20.3% of patients with ischemic stroke died. A number of factors were independently associated with 28-day mortality; the two strongest independent predictors were depressed level of consciousness on presentation and hemorrhagic stroke type. While virtually all patients completed a CT during the admission, evidence-based processes of care such as anti-thrombotic therapy and carotid ultrasound for ischemic stroke patients were underutilized.

Conclusions

This cohort study highlights the high mortality due in part to the large proportion of hemorrhagic strokes in Vietnam. Lack of hypertension awareness and standards of care exacerbated clinical outcomes. Numerous opportunities for simple, inexpensive interventions to improve outcomes or reduce recurrent stroke have been identified.

     

Correlation between quantitative analysis of wall shear stress and intima-media thickness in atherosclerosis development in carotid arteries

Background

This paper presents quantitative analysis of blood flow shear stress by measuring the carotid arterial wall shear stress (WSS) and the intima-media thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly basis in order to cause atherosclerosis.

Methods

This study is based on establishing an atherosclerosis model of high-fat rabbits, and measuring the rabbits’ common carotid arterial WSS of the experimental group and control group on a weekly basis. Detailed analysis was performed by using WSS quantification.

Results

We have demonstrated small significant difference of rabbit carotid artery WSS between the experimental group and the control group (P<0.01) from the 1st week onwards, while the IMT of experimental group had larger differences from 5th week compared with the control group (P<0.05). Next, we have shown that with increasing blood lipids, the rabbit carotid artery shear stress decreases and the rabbit carotid artery IMT goes up. The decrease of shear stress appears before the start of IMT growth. Furthermore, our receiver operator characteristic (ROC) curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm², the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and the specificity is 81.3%. The area under the ROC curve is 0.9283.

Conclusions

All these data goes to show that WSS decreasing to 1.198 dyne/cm² can be used as an indicator that rabbit common carotid artery comes into the period of fibrous plaques. In conclusion, our study is able to find and confirm that the decrease of the arterial WSS can predict the occurrence of atherosclerosis earlier, and offer help for positive clinical intervention.

     

Ischemic stroke incidence in Santa Coloma de Gramenet (ISISCOG), Spain. A community-based study

Background

In Spain, stroke is one of the major causes of death and the main cause of severe disability in people over 65 years. We analyzed the incidence of ischemic stroke, stroke subtypes, case fatality and disability at 90 days after the event in a Spanish population.

Methods

A prospective community-based register of ischemic strokes was established in Santa Coloma de Gramenet (Barcelona) [116,220 inhabitants of all ages, according to the municipal census of December 31,2001], from January 1 to December 31, 2003.Standard definitions and case finding methods were used to identify all cases in all age groups. Every patient underwent a complete clinical evaluation and systematic tests including neuroimaging (CT/MRI) and vascular studies (carotid duplex ultrasound intra and extracranial and MR angiography).

Results

Over a one year period, 196 ischemic strokes were registered [107 men; median age = 76 years (range 39–98)], being the first event in 159 patients (81.1%) and a recurrent stroke in 37 (18.9%). After age-adjustment to the European population, the incidence of ischemic stroke per 100,000 inhabitants was 172 (95% CI, 148–196); 219 (176–261) in men and 133 (105–160) in women, with an annual incidence for first ischemic stroke of 139 (118–161); 165 (128–201) in men and 115 (89–140) in women. The incidence of stroke increased with age.Stroke subtypes (TOAST classification criteria) were lacunar in 28.8%, atherothrombotic in 18.6%, cardioembolic in 26.6% and undetermined in 26.0% of patients. At 90 days, the case-fatality was 12%, and among survivors, moderate-to-severe disability was present in 45 % at 3 months.

Conclusion

This prospective community-based study shows one of the lowest incidences of stroke in Europe, as well as one of the lowest case fatality and disability rates at 90 days after stroke.

     

Prospective assessment of cardiovascular risk parameters in patients with rheumatoid arthritis

Background

The study presents a prospective follow-up assessment of cardiovascular (CV) risk parameters in patients with rheumatoid arthritis (RA) in comparison with control subjects.

Methods

The study group consisted of 41 RA patients. The following parameters were assessed at subsequent visits [initial (T0), follow-up after 6 years (T6)]: traditional CV risk factors, carotid intima media thickness (cIMT), QTc duration, serum concentration of amino-terminal pro-brain natriuretic peptide (NT-proBNP). A comparative cIMT assessment was performed on 23 healthy controls of comparable age.

Results

The mean (SD) cIMT value in RA patients was significantly higher at T6 than at T0 [0.87 (0.21) vs 0.76 (0.15) mm, p?<?0.001], the increase in patients with atherosclerotic plaques was noted. Patients with plaques were significantly older, had higher inflammatory parameters. The mean cIMT was significantly higher in RA patients than in controls at both T6, T0 visits. Certain traditional CV risk factors exacerbated during follow up. Unfavorable metabolic parameters and significantly higher cIMT were found in male patients than in female patients at T6. During follow-up, no significant differences in NT-proBNP, QTc were found. There were no significant relationships between cIMT, NT-proBNP, QTc and parameters of disease activity at T6.

Conclusions

During the 6-year course of established RA, significant exacerbation of atherosclerosis was found, revealed by higher cIMT. A careful monitoring should be applied to patients with atherosclerotic plaques and of male gender due to higher burden of CV risk. In long-standing disease, traditional CV risk factors seem to play a key role, beyond the inflammatory activity.

     

Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion

Objective

Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.

Methods

A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).

Results

There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = ?0.210, p = 0.006).

Conclusions

Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Recurrent posterior circulation infarction caused by anomalous occipital bony process in a young patient

Background

Structural anomaly of the cervical spine or craniocervical junction has been reported as one of the rare causes of ischemic stroke. We report a case of a young patient with recurrent posterior circulation infarction that may have been associated with an anomalous occipital bony process compressing the vertebral artery.

Case presentation

A 23-year-old man experienced recurrent posterior circulation infarction 5 times over a period of 5 years. He had no conventional vascular risk factors. Young age stroke work-up including thorough cardiac, intra- and extracranial vascular evaluation and laboratory tests for the hypercoagulable state or connective tissue disease yielded unremarkable results. An anomalous bony process from the occipital base compressing the left vertebral artery was observed on brain CT. All the recurrent strokes were explainable by the arterial thromboembolism originating from the compressed left vertebral artery. Therefore, the left vertebral artery compressed by the anomalous occipital bony process may have been the culprit behind the recurrent thromboembolic strokes in our patient. Intractable recurrent strokes even under optimal medical treatment led us to make a decision for the intervention. Instead of surgical removal of the anomalous occipital bony process, the left vertebral artery was occluded permanently by endovascular coiling after confirming that this would cause no neurological deficits or flow disturbance in the posterior circulation. There was no recurrence of stroke for 2 years after permanent occlusion of the left vertebral artery.

Conclusion

Arterial thromboembolism originating from the left vertebral artery compressed by the anomalous occipital bony process is a rare but not to be overlooked cause of posterior circulation infarction. When intractable to medical treatment, endovascular occlusion of the vertebral artery without flow disturbance to the posterior circulation may be a useful treatment option when surgical removal is not feasible.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Etiology of isolated pontine infarctions: a study based on high-resolution MRI and brain small vessel disease scores

Background

In this retrospective study, we investigated the main pathogenesis of the two types of isolated pontine infarction: paramedian pontine infarcts (PPIs) and small deep pontine infarcts (SDPIs).

Methods

Acute ischemic stroke patients, comprising 117 PPI patients and 40 SDPI patients, were enrolled. High-resolution magnetic resonance imaging (HR-MRI) and routine MRI sequences were performed for each patient, and clinical data were collected. The following brain small vessel disease (SVD) features of the MRI scans were each rated (0 or 1) separately: asymptomatic lacunar infarcts, white matter lesions (WMLs), deep and infratentorial cerebral microbleeds (CMBs), and enlarged perivascular spaces in the basal ganglia. The ratings were also summed in an ordinal “SVD score” (range: 0–4). The difference in the SVD score between the PPI and SDPI groups was determined. The presence and location of basilar artery (BA) atherosclerotic plaques (based on HR-MRI) in the two groups was evaluated.

Results

There was a significant difference in the total SVD score and three of the four independent SVD features (asymptomatic lacunar infarcts, WMLs, and deep and infratentorial CMBs) between the two groups. The prevalence of BA plaques relevant to the infarcts in the PPI group was significantly higher than that in the SDPI group, whereas the prevalence of plaques irrelevant to the infarcts was similar between the two groups. The degree of BA stenosis was slightly higher in the PPI group than in the SDPI group. Diabetes mellitus was much more prevalent in the PPI group. The National Institute of Health Stroke Scale score was higher in the PPI group, which is in accordance with the larger infarct size in the PPI group.

Conclusion

BA atherosclerosis may be the major cause of PPI, while SVD may be the main mechanism underlying SDPI. HR-MRI combined with the total SVD score should be helpful to explore the pathogenesis underlying isolated pontine infarctions, especially in cases involving low-grade BA stenosis.

     

Genetic susceptibility to dyslipidemia and incidence of cardiovascular disease depending on a diet quality index in the Malmö Diet and Cancer cohort

Background

By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk.

Methods

We included 24,799 participants (62 % women, age 44–74 years) from the Malmö Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants’ dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose.

Results

The GRS_LDL-C (P?=?5?×?10^?6) and GRS_HDL-C (P?=?0.02) but not GRS_TG (P?=?0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk (P?>?0.39). A high compared to a low diet quality attenuated the association between GRS_LDL-C and the risk of incident ischemic stroke (P interaction?=?0.01).

Conclusion

We found some evidence of an interaction between diet quality and GRS_LDL-C on ischemic stroke.

     

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.

     

Neuroprotective effects of amiodarone in a mouse model of ischemic stroke

Background

Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice.

Methods

Focal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation.

Results

Amiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9?±?2.1% hemisphere [mean?±?SD] vs. 11.2?±?1.4%; P?<?0.05) and improved functional outcomes: lower asymmetric body swing rates (52?±?17% vs. 65?±?18%; P?<?0.05) and fewer left turns (7.1?±?1.2 vs. 8.3?±?1.2; P?<?0.05). In contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The neuroprotective effect of amiodarone pre-treatment was abolished by co-administration of veratrine but not by isoproterenol.

Conclusions

Amiodarone pre-treatment attenuated ischemic brain injury and improved functional outcomes without affecting heart rhythm and blood pressure. The present results showed that amiodarone pre-treatment has neuroprotective effects, at least in part, via blocking the sodium channels.