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.

     

Excess mortality and morbidity during the July 2006 heat wave in Porto, Portugal

The purpose of this study was to understand the effects of the July 2006 heat wave through the use of the heat index, in mortality (all causes) and morbidity (all causes, respiratory and circulatory diseases) in general, and in people over 74 years and by gender, in Porto. In this paper, the Poisson generalized additive regression model was used to estimate the impact of apparent temperature (heat index) and daily mortality and morbidity during the July 2006 heat wave. Daily mortality, morbidity and heat index were correlated with lags of apparent temperature up to 7 days using Pearson correlation. For a 1°C increase in mean apparent temperature we observed a 2.7 % (95 % CI: 1.7–3.6 %) increase in mortality (all cause), a 1.7 % (95 % CI: 0.6–2.9 %) increase in respiratory morbidity, a 2.2 % (95 % CI: 0.4–4.1 %) increase in respiratory morbidity in women, a 5.4 % (95%CI: 1.1–6.6 %) increase in chronic obstructive pulmonary morbidity, and a 7.5 % (95 % CI: 1.3–14.1 %) increase in chronic obstructive pulmonary morbidity in women, for the entire population. For people?≥?75 years, our results showed a 3.3 % increase (95 % CI: 1.7–5.0 %) in respiratory morbidity, a 2.7 % (95 % CI: 0.4–5.1 %) increase in respiratory morbidity in men, a 3.9 % (95 %CI: 1.6–6.3 %) increase in respiratory morbidity in women, a 7.0 % (95 % CI: 1.1–13.2 %) in chronic obstructive pulmonary disease, and a 9.0 % (95 % CI: 0.3–18.5 %) in chronic obstructive pulmonary disease in women. The use of heat index in a Mediterranean tempered climate enabled the identification of the effects of the July 2006 heat wave in mortality due to all causes and in respiratory morbidity of the general population, as well as in respiratory morbidity of individuals with more than 74 years of age.     

Some epidemiologic and clinical problems in ischemic cerebral stroke

The study involved 739 patients with the ischemic cerebral stroke into two groups: with reversible and irreversible ischemic cerebral stroke. General characteristics of patients (incidence, sex, age etc.) was similar to the characteristics of patients from other centres. Morbidity rate for ischemic cerebral strokes was 93.9, including reversible stroke 21.3 and other 72.6; mortality factor 47.2, and mortality rate 29.6%. An increase in morbidity for irreversible stroke in women over 80 years of age is striking. The authors suggest that the classification of cerebral strokes should include reversible strokes whereas progressive stroke should not be considered distinguished entity.     

Effects of diurnal variations in temperature on non-accidental mortality among the elderly population of Montreal,Québec, 1984–2007

The association between ambient temperature and mortality has been studied extensively. Recent data suggest an independent role of diurnal temperature variations in increasing daily mortality. Elderly adults—a growing subgroup of the population in developed countries—may be more susceptible to the effects of temperature variations. The aim of this study was to determine whether variations in diurnal temperature were associated with daily non-accidental mortality among residents of Montreal, Québec, who were 65 years of age and over during the period between 1984 and 2007. We used distributed lag non-linear Poisson models constrained over a 30-day lag period, adjusted for temporal trends, mean daily temperature, and mean daily concentrations of nitrogen dioxide and ozone to estimate changes in daily mortality with diurnal temperature. We found, over the 30 day lag period, a cumulative increase in daily mortality of 5.12 % [95 % confidence interval (CI): 0.02–10.49 %] for a change from 5.9 °C to 11.1 °C (25th to 75th percentiles) in diurnal temperature, and a 11.27 % (95%CI: 2.08–21.29 %) increase in mortality associated with an increase of diurnal temperature from 11.1 to 17.5 °C (75th to 99th percentiles). The results were relatively robust to adjustment for daily mean temperature. We found that, in Montreal, diurnal variations in temperature are associated with a small increase in non-accidental mortality among the elderly population. More studies are needed in different geographical locations to confirm this effect.     

Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke

The aim of this study was to examine whether the circulating CXC chemokine ligand-12 (CXCL12) level can predict a 6-month outcome in Chinese patients with acute ischemic stroke (AIS). In a prospective study, CXCL12 levels were measured on admission in the serum of 304 consecutive patients with AIS. The prognostic value of CXCL12 to predict the functional outcome and mortality within 1 year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. A receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in predicting functional outcome and mortality. Patients with an unfavorable outcome and non-survivors had significantly increased CXCL12 levels on admission (P?<?0.0001 and P?<?0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CXCL12 (≥12.4 ng/mL; third quartile) was an independent predictor of functional outcome (odds ratio [OR]?=?8.81; 95 % confidence interval [CI] 4.92–24.79) and mortality (OR?=?10.15; 95 %CI 2.44–27.98). The area under the receiver operating characteristic curve of CXCL12 was 0.84 (95 % CI 0.76–0.92) for functional outcome and 0.87 (95 % CI 0.80–0.93) for mortality. Circulating CXCL12 serum levels at admission is a useful and complementary biomarker to predict functional outcome and mortality 6 months after acute ischemic stroke.     

Temperature variation and emergency hospital admissions for stroke in Brisbane,Australia, 1996–2005

Stroke is a leading cause of disability and death. This study evaluated the association between temperature variation and emergency admissions for stroke in Brisbane, Australia. Daily emergency admissions for stroke, meteorologic and air pollution data were obtained for the period of January 1996 to December 2005. The relative risk of emergency admissions for stroke was estimated with a generalized estimating equations (GEE) model. For primary intracerebral hemorrhage (PIH) emergency admissions, the average daily PIH for the group aged < 65 increased by 15% [95% confidence interval (CI): 5, 26%] and 12% (95% CI: 2, 22%) for a 1°C increase in daily maximum temperature and minimum temperature in summer, respectively, after controlling for potential confounding effects of humidity and air pollutants. For ischemic stroke (IS) emergency admissions, the average daily IS for the group aged ≥ 65 decreased by 3% (95% CI: −6, 0%) for a 1°C increase in daily maximum temperature in winter after adjustment for confounding factors. Temperature variation was significantly associated with emergency admissions for stroke, and its impact varied with different type of stroke. Health authorities should pay greater attention to possible increasing emergency care for strokes when temperature changes, in both summer and winter.     

Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case–control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46–7.68], OR 6.63 [4.26–10.31], and OR 3.03 [2.04–4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders.     

The prognostic value of biomarkers in stroke

Background

Ischemic injury triggers inflammatory cascades and changes in the protein synthesis, neurotransmitters and neuro-hormones in the brain parenchyma that may further amplify the tissue damage. The “Triage® Stroke Panel”, a biochemical multimarker assay, detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase-9 (MMP-9), and S100β protein generating a Multimarker index of these values (MMX). The aims of this prospective study in consecutive patients with ischemic or hemorrhagic stroke were to assess: 1) the rate of an increase of biomarkers (BNP, D-dimer, MMP-9 and S-100β) tested with the Triage Stroke Panel; 2) the correlation between the increase of these biomarkers and functional outcome at 4 months; 3) the risk factors for the increase of biomarkers.

Methods

The outcome of the study was 120-day mortality and it was compared in patients with Stroke Panel >4 and ≤4. Multiple logistic regression analyses were performed to identify independent predictors for death and for the increase of biomarkers.

Results

244 consecutive patients (mean age 73.02 years; 53.7 % males) were included in the study; 210 ischemic strokes and 34 hemorrhagic strokes. 161/244 (66.0 %) had an increase of biomarkers. At 120 days, 85 patients had died (34.8 %). Death was seen in 68/161 patients with an increase of biomarkers (42.2 %) compared with 17/83 patients without (20.5 %). Regression logistic analysis found that a Stroke Panel >4 (OR 3.1; 95 % CI 1.5–6.2, p?=?0.002) was associated with mortality. The increase of biomarkers was independently predicted by an increase of PCR on admission (OR 2.9, 95 CI 1.4–6.0, p?=?0.003).

Conclusions

An increase of biochemical markers such as BNP, D-Dimers, MMP-9, and S100β tested with a Triage Stroke Panel (>4) was correlated with mortality at 120 days from stroke onset.

     

Elevated Serum and Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Unfavorable Functional Outcome in Subjects with Acute Ischemic Stroke

The aim of this study was to evaluate the prognostic value of serum and cerebrospinal fluid (CSF) free fatty acid (FFA) levels in a cohort of patients with an acute ischemic stroke (AIS). In a prospective study, FFA levels were measured using an enzyme cycling method on admission in serum and CSF of 252 consecutive patients with AIS. The prognostic value of FFA to predict the functional outcome and mortality within 90-day was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Serum and CSF levels of FFA increased with increasing severity of stroke as defined by the NIHSS score (all P?<?0.001). Patients with an unfavorable outcomes and non-survivors had significantly increased FFA serum and CSF levels on admission (all P?<?0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that serum FFA ≥0.71 mmol/L (third quarters) was an independent predictor of functional outcome (odds ratios (OR)?=?4.86; 95 % confidence interval (CI) 2.26–10.48) and mortality (OR?=?7.72; 95 % CI 3.01–21.48). The area under the receiver operating characteristic curve of serum FFA was 0.79 (95 % CI, 0.72–0.86) for functional outcome and 0.86 (95 % CI, 0.78–0.94) for mortality. Similarly, CSF FFA level also was an indicator for predicting of functional outcome and mortality. FFA levels in serum and CSF may serve as independent biomarkers in addition of the traditional methods for assessing the functional outcome and mortality of AIS.     

Analysis of Risk Factors of Hemorrhagic Transformation After Acute Ischemic Stroke: Cerebral Microbleeds Do Not Correlate with Hemorrhagic Transformation

To study the potential risk factors including cerebral microbleeds (CMB) of hemorrhagic transformation (HT) after acute ischemic stroke. We included 348 consecutive patients with acute infarction who were hospitalized in two centers from June 2009 to December 2010. Acute ischemic infarctions were subdivided into atherosclerotic, cardioemblic, lacunar, and undetermined infarction groups. The related risk factors were recruited for analysis. All patients underwent gradient-echo T2-weighted imaging (GRE) to detect CMB and HT. Logistic regression analysis was used to analyze relationships, with HT as response variable and potential risk factors as explanatory variables. Multivariate logistic regression analysis demonstrated that predictor factors of HT were cardioembolic infarction (OR 24.956, 95 % CI 2.734–227.801, P = 0.004), infarction of undetermined causes (OR 19.381, 95 % CI 1.834–205.104, P = 0.014), and scores of NIHSS (OR 1.187, 95 % CI 1.109–1.292, P < 0.001), diabetes mellitus (OR 4.973, 95 % CI 2.004–12.338, P = 0.001). Whereas, the level of low-density lipoprotein was the protective factor (OR 0.654, 95 % CI 0.430–0.996, P = 0.048).The prevalence of CMB was 45.98 % (160/348) with no statistically difference among different subtypes. Thirty-five out of 348 (10.06 %) patients with ischemic stroke developed HT with a statistical difference among different subtypes of ischemia (χ ² = 42.140, P < 0.001). The distributions of HI and PH among subgroups were variable with significant differences (χ ² = 17.536, P = 0.001; χ ² = 12.028, P = 0.007). PH frequency of cardioembolism was the highest (4/28, 14.29 %), and symptomatic ICH was also highest (7.14 %). The CMBs do not significantly correlate with HT. Knowledge of the risk factors associated with HT after ACI, especially HT following thrombolyitc therapy may provide insight into the mechanisms underlying the development of HT, helps to develop treatment strategy that reduces the risk of PH and implicates for the design of future acute ischemic stroke trials.     

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.

     

Modifiable Etiological Factors and the Burden of Stroke from the Rotterdam Study: A Population-Based Cohort Study

Background

Stroke prevention requires effective treatment of its causes. Many etiological factors for stroke have been identified, but the potential gain of effective intervention on these factors in terms of numbers of actually prevented strokes remains unclear because of the lack of data from cohort studies. We assessed the impact of currently known potentially modifiable etiological factors on the occurrence of stroke.

Methods and Findings

This population-based cohort study was based on 6,844 participants of the Rotterdam Study who were aged ≥55 y and free from stroke at baseline (1990–1993). We computed population attributable risks (PARs) for individual risk factors and for risk factors in combination to estimate the proportion of strokes that could theoretically be prevented by the elimination of etiological factors from the population.The mean age at baseline was 69.4 y (standard deviation 6.3 y). During follow-up (mean follow-up 12.9 y, standard deviation 6.3 y), 1,020 strokes occurred. The age- and sex-adjusted combined PAR of prehypertension/hypertension, smoking, diabetes mellitus, atrial fibrillation, coronary disease, and overweight/obesity was 0.51 (95% CI 0.41–0.62) for any stroke; hypertension and smoking were the most important etiological factors. C-reactive protein, fruit and vegetable consumption, and carotid intima-media thickness in combination raised the total PAR by 0.06. The PAR was 0.55 (95% CI 0.41–0.68) for ischemic stroke and 0.70 (95% CI 0.45–0.87) for hemorrhagic stroke.The main limitations of our study are that our study population comprises almost exclusively Caucasians who live in a middle and high income area, and that risk factor awareness is higher in a study cohort than in the general population.

Conclusions

About half of all strokes are attributable to established causal and modifiable factors. This finding encourages not only intervention on established etiological factors, but also further study of less well established factors. Please see later in the article for the Editors'' Summary     

Measures of Adiposity and Risk of Stroke in China: A Result from the Kailuan Study

Objective

The objective of this study was to explore the association between adiposity and risk of incident stroke among men and women.

Methods

We studied the relationship between adiposity and stroke among 94,744 participants (18–98 years old) in the Kailuan study. During a follow-up of 4 years, 1,547 ischemic or hemorrhagic strokes were recorded. Measurements of adiposity included body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated from Cox regression models and each model fit was assessed using −2log-likelihood.

Results

Every measurement of adiposity was associated with the risk for total stroke and ischemic stroke, but not for hemorrhagic stroke. After adjusting for confounders and intermediates, the HR (comparing the mean of the highest quintile with that of the lowest quintile) for total stroke was 1.34(1.13–1.60) for BMI, 1.26(1.06–1.52) for WC, 1.29(1.08–1.56) for WHpR, and 1.38(1.15–1.66) for WHtR. The HR for ischemic stroke was 1.52(1.24–1.88) for BMI, 1.46(1.17–1.81) for WC, 1.40(1.12–1.74) for WHpR, and 1.62(1.29–2.04) for WHtR. The model fit for each of the indices was similar.

Conclusions

Adiposity increases the total risk of stroke and ischemic stroke, but not of hemorrhagic stroke. No clinically meaningful differences among the associations between BMI, WC, WHpR, and WHtR and stroke incidence were identified in this study.     

The impact of heat,cold, and heat waves on hospital admissions in eight cities in Korea

Although the impact of temperature on mortality is well documented, relatively fewer studies have evaluated the associations of temperature with morbidity outcomes such as hospital admissions, and most studies were conducted in North America or Europe. We evaluated weather and hospital admissions including specific causes (allergic disease, asthma, selected respiratory disease, and cardiovascular disease) in eight major cities in Korea from 2003 to 2008. We also explored potential effect modification by individual characteristics such as sex and age. We used hierarchical modeling to first estimate city-specific associations between heat, cold, or heat waves and hospitalizations, and then estimated overall effects. Stratified analyses were performed by cause of hospitalization, sex, and age (0–14, 15–64, 65–74, and ≥75 years). Cardiovascular hospitalizations were significantly associated with high temperature, whereas hospitalizations for allergic disease, asthma, and selected respiratory disease were significantly associated with low temperature. The overall heat effect for cardiovascular hospitalization was a 4.5 % (95 % confidence interval 0.7, 8.5 %) increase in risk comparing hospitalizations at 25 to 15 °C. For cold effect, the overall increase in risk of hospitalizations comparing 2 with 15 °C was 50.5 (13.7, 99.2 %), 43.6 (8.9, 89.5 %), and 53.6 % (9.8, 114.9 %) for allergic disease, asthma, and selected respiratory disease, respectively. We did not find statistically significant effects of heat waves compared with nonheat wave days. Our results suggest susceptible populations such as women and younger persons. Our findings provide suggestive evidence that both high and low ambient temperatures are associated with the risk of hospital admissions, particularly in women or younger person, in Korea.     

MMP-9 Inhibition: a Therapeutic Strategy in Ischemic Stroke

Ischemic stroke is a leading cause of disability worldwide. In cerebral ischemia there is an enhanced expression of matrix metallo-proteinase-9 (MMP-9), which has been associated with various complications including excitotoxicity, neuronal damage, apoptosis, blood–brain barrier (BBB) opening leading to cerebral edema, and hemorrhagic transformation. Moreover, the tissue plasminogen activator (tPA), which is the only US-FDA approved treatment of ischemic stroke, has a brief 3 to 4 h time window and it has been proposed that detrimental effects of tPA beyond the 3 h since the onset of stroke are derived from its ability to activate MMP-9 that in turn contributes to the breakdown of BBB. Therefore, the available literature suggests that MMP-9 inhibition can be of therapeutic importance in ischemic stroke. Hence, combination therapies of MMP-9 inhibitor along with tPA can be beneficial in ischemic stroke. In this review we will discuss the current status of various strategies which have shown neuroprotection and extension of thrombolytic window by directly or indirectly inhibiting MMP-9 activity. In the introductory part of the review, we briefly provide an overview on ischemic stroke, commonly used models of ischemic stroke and a role of MMP-9 in ischemia. In next part, the literature is organized as various approaches which have proven neuroprotective effects through direct or indirect decrease in MMP-9 activity, namely, using biotherapeutics, involving MMP-9 gene inhibition using viral vectors; using endogenous inhibitor of MMP-9, repurposing of old drugs such as minocycline, new chemical entities like DP-b99, and finally other approaches like therapeutic hypothermia.     

Meteorological factors are associated with hemorrhagic fever with renal syndrome in Jiaonan County,China, 2006–2011

This study examined the effect of meteorological factors on the occurrence of hemorrhagic fever with renal syndrome (HFRS) using a generalized additive model with penalized smoothing splines in Jiaonan, China, from 2006 to 2011. The dose–response relationship was first examined, and then the association between daily meteorological variables and HFRS occurrence was investigated according to the dose–response curves. There were two linear segments in the temperature–HFRS relationship curve. When daily temperature was lower than 17 °C, a positive association was found [with excessive risk (ER) for 1 °C increase on the current day being 2.56 %, 95 % confidence interval (CI): 0.36 % to 4.80 %]. An inverse association was found when daily temperature was higher than 17 °C [ER for 1 °C increase on the current day was ?12.82 % (95 % CI: ?17.51 % to ?7.85 %)]. Inverse associations were observed for relative humidity [ER for 1 % increase on lag day 4 was ?1.21 % (95 % CI: ?1.63 % to ?0.79 %)] and rainfall [ER for 1 mm increase on lag day 1 was ?2.20 % (95 % CI: ?3.56 % to ?0.82 %)]. Meteorological factors might be important predictor of HFRS epidemics in Jiaonan County.     

Tetrandrine Attenuated Cerebral Ischemia/Reperfusion Injury and Induced Differential Proteomic Changes in a MCAO Mice Model Using 2-D DIGE

Ischemic stroke is the most common type of stroke and brings about a big disease burden because of high mortality and disability in China. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to possess anti-inflammatory and free radical scavenging effects and even regulate astrocyte activation, but the possible role of tetrandrine in ameliorating cerebral ischemia/reperfusion injury of ischemic stroke remains unknown. The aim of this study was to determine the effects of tetrandrine on neurological injury and differential proteomic changes induced by transient reversible middle cerebral artery occlusion (MCAO) in mice. Male Balb/c mice were divided into sham (n = 30), MCAO + saline as control (n = 30), and MCAO + Tet as tetrandrine-treated (n = 30) groups. Mice in the control and tetrandrine-treated groups underwent 120 min of MCAO following reperfusion. Immediately and 2 h after MCAO, the mice received either normal saline (sham operated and control groups) or tetrandrine (tetrandrine-treated group) intraperitoneally. Neurological defects, brain water content, and infarct volume at 24 h after stoke were used to evaluate neurological injury extent. Treatment with tetrandrine not only mitigated cerebral neurological deficits (P < 0.05) and infarct size (P < 0.01), but also decreased brian edema in the ischemic brain (P < 0.05). Then, fluorescence two-dimensional difference in gel electrophoresis was used to detect our systematic differential profiling of proteomic changes responding to tetrandrine administration. We validated that the expression of GRP78, DJ-1 and HYOU1 was associated with neuroprotective effect of tetrandrine in MCAO model by Western blotting. These findings indicate a potential neuroprotective role of tetrandrine for ischemic stroke and yield insights into cellular and molecular mechanisms of tetrandrine taking place in ischemic stroke.     

The influence of meteorological and geomagnetic factors on acute myocardial infarction and brain stroke in Moscow,Russia

Evidence of the impact of air temperature and pressure on cardiovascular morbidity is still quite limited and controversial, and even less is known about the potential influence of geomagnetic activity. The objective of this study was to assess impacts of air temperature, barometric pressure and geomagnetic activity on hospitalizations with myocardial infarctions and brain strokes. We studied 2,833 myocardial infarctions and 1,096 brain strokes registered in two Moscow hospitals between 1992 and 2005. Daily event rates were linked with meteorological and geomagnetic conditions, using generalized linear model with controls for day of the week, seasonal and long-term trends. The number of myocardial infarctions decreased with temperature, displayed a U-shaped relationship with pressure and variations in pressure, and increased with geomagnetic activity. The number of strokes increased with temperature, daily temperature range and geomagnetic activity. Detrimental effects on strokes of low pressure and falling pressure were observed. Relative risks of infarctions and strokes during geomagnetic storms were 1.29 (95 % CI 1.19–1.40) and 1.25 (1.10–1.42), respectively. The number of strokes doubled during cold spells. The influence of barometric pressure on hospitalizations was relatively greater than the influence of geomagnetic activity, and the influence of temperature was greater than the influence of pressure. Brain strokes were more sensitive to inclement weather than myocardial infarctions. This paper provides quantitative estimates of the expected increases in hospital admissions on the worst days and can help to develop preventive health plans for cardiovascular diseases.     

The apoptotic actions of platelets in acute ischemic stroke

Stroke is a disease that affects the blood vessels that supply blood to the brain. Although platelets are implicated in the pathophysiology of stroke the mechanism is still not clear and there antiplatelet agents available for the prevention and treatment of stroke. We herein examined the relationship between the potential cytokine, TNF-α platelet activation and apoptosis in acute ischemic stroke patients. We selected 60 patients (mean age 57.9 ± 10.2 years) who had not taken any antiplatelet drugs for 14 days. A group of 45 participants (mean age 51.05 ± 9.07 years) were selected as the control group. For both the patients and for the control group, P-selectin (CD62p) and Annexin-V binding, cytochrome-c levels, caspase-3 gene expression and caspase-3 releasing and plasma TNF-α levels were measured in platelets. The results showed significant increase in plasma TNF-α and platelet Annexin-V, CD62p, cytochrome-c and caspase-3 gene expression in stroke patients compared to the control group. The data of this work suggests that inflammation may have a role in platelet apoptosis in stroke which may suggest a new aspect of the role of inflammation in the development of acute ischemic stroke.     

Clinical Significance of Cerebral Microbleeds Locations in CADASIL with R544C NOTCH3 Mutation

MethodsThis is a cohort study of patients who were diagnosed with genotype-confirmed R544C-mutation CADASIL. Primary neurologic symptoms were recorded. Symptomatic strokes were defined as transient ischemic attack, ischemic strokes and hemorrhagic strokes. CMBs were defined as focal areas of round signal loss on T2*-weighted gradient echo planar images with a diameter of less than 10 mm. The locations of CMBs were divided into lobar, basal ganglia, thalamus, brain stem and cerebellum. Multiple logistic regressions were performed to identify the epidemiologic or vascular risk factors associated with symptomatic stroke in patients with CADASIL.ResultsAmong total of 51 subjects in this cohort, CMBs were present in 20 of 32 patients (64.5%) in the symptomatic stroke-group and in 8 of 19 patients (42.1%) in the non-stroke group (p = 0.16). CMBs were observed more frequently in the basal ganglia (p<0.001) and the cerebellum (p<0.018) in the symptomatic stoke group compared to the non-stroke group. The mean number of CMBs was significantly higher in the symptomatic stroke group (15.4±18.0 lesions per patients with CMBs) versus those without symptomatic stroke (3.3±3.0 lesions per patients with CMBs) (p = 0.003). Hypertension was an independent risk factor for symptomatic stroke in CADASIL (p = 0.014). It was independently associated with CMBs locations as basal ganglia (p = 0.016), thalamus (p = 0.010), brainstem (p = 0.044), and cerebellum (p = 0.049). However, It was not independently associated with CMBs on lobar lesion (p = 0.152).ConclusionsIn this study hypertension was an independent predictor of CMBs presence in specific brain locations, as well as symptomatic stroke in the CADASIL patients. The distribution and burden of CMBs might be a clinically useful marker for the risk of symptomatic stroke. However, further prospective studies on the relationship between CMBs distribution and symptomatic stroke are required in order to support these preliminary findings.