Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature

Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992–2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9–6.9 %) in Seoul, 4.1 % (95 % CI, 1.6–6.6 %) in Incheon, 2.3 % (?0.2 to 5.0 %) in Daegu and 3.6 % (0.7–6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.     

Decompressive Hemicraniectomy in a South American Population – Morbidity and Outcomes Analysis

Background

Malignant cerebral artery strokes have a poor prognosis, with nearly 80% of mortality in some series despite intensive care. After a large randomized trial, decompressive hemicraniectomy has been performed more often in stroke patients. Here, we describe patients in a tertiary teaching hospital in Brazil, emphasizing the impact of age on outcomes.

Methods

A retrospective cohort of patients, with malignant strokes which received a decompressive hemicraniectomy, from paper and electronic medical records, from January 2010 to December 2013 was divided into two groups according to age.

Results

The final analysis included 60 patients. The overall mortality was higher among patients older than 60 yrs (67% vs. 41%; p = 0.039), whose group also had a worse outcome (76% with mRS 5 or 6) at 90 days (OR 3.91 CI95% 1.30–11.74), whereas only 24% had mRS of 0–4 (p = 0.015). All patients who presented with sepsis died (p = 0.003). The incidence of pulmonary infection was very high in the elderly group (76%) with significant intergroup differences (p = 0.027, OR 8.32 CI95% 0.70–98.48).

Conclusions

Older patients present more commonly with infections, more disabilities and a higher mortality, highlighting very poor results in elderly population. These results should be proved with a South American trial, and if confirmed, it can impact on future decisions regarding decompressive craniectomy for acute ischemic stroke in our region.     

The influence of proglumide, a putative CCK antagonist, on cerebral ischemia in gerbil

Studies were conducted to clarify the possible role of CCK in cerebral ischemia and to evaluate the effects of proglumide, a competitive and reversible CCK antagonist, as a potential therapeutic or prophylactic tool in the treatment of cerebral ischemia. Proglumide at the doses of 10, 50 and 150 mg/kg was administered to gerbils before unilateral carotid ligation, and its effect on stroke index score, incidence and mortality rate was observed. Our results show that proglumide injected prior to carotid ligation at the dose of 150 mg/kg significantly reduces both incidence and mortality rate and changes the distribution of the stroke index score in gerbils. There was a significant inverse relationship between the dose of proglumide and both incidence and mortality: the greater the injection dose of proglumide, the lower the incidence and mortality. These results suggest that CCK may be involved in the pathological processes of cerebral ischemia and proglumide or related compounds prove to be effective in the pharmacological prophylaxis of ischemic brain damage.     

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.

     

Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy

Dyscirculatory encephalopathy and mild ischemic stroke are characterized by solitary changes in components of glutathione metabolism. In moderate and severe ischemic strokes essential changes have been found. Changes in glutathione metabolism are also expressed in hemorrhagic stroke. The clearest increase was found in activities of glutathione peroxidase and glutathione transferase and in rare cases in activities of glutathione reductase and GSH concentration. The increase of enzymes activity was not found in patients with delayed onset of treatment (more than 3 days) and also in severe cases terminated by subsequent death of patients. Glutathione system is obviously important for tolerance to cerebral ischemia.     

炎症标记物与缺血性中风预后评价

缺血性中风触发的炎症反应是一个级联放大过程,不仅可直接对缺血脑组织造成继发性损伤,还可通过与其他病理生理通路的相互影响、相互促进,共同对缺血后脑组织造成不可逆损伤。因此,采用炎症标记物对脑缺血损伤及其预后进行评价,具有重要临床意义。临床研究发现,多炎症标记物法用于缺血性中风的诊治和预后评价比单炎症标记物法更全面、更准确,故更具明显优势。综述脑缺血引发的炎症机制、脑缺血所致炎症通路与其他病理生理通路( 如氧化应激、细胞凋亡和兴奋性毒性) 的关联以及炎症标记物在缺血性中风预后评价中的应用。     

Gender Differences in 1-Year Clinical Characteristics and Outcomes after Stroke: Results from the China National Stroke Registry

Background

Previous reports have shown inconsistent results on clinical outcomes between women and men after stroke, and little is known about gender differences on outcomes in Chinese post-stroke patients. The aim of this study was to explore whether there were gender differences on clinical characteristics and outcomes in Chinese patients after ischemic stroke by using the data from the China National Stroke Registry (CNSR).

Methods and Findings

Out of 12,415 consecutively recruited patients with acute ischemic stroke in the CNSR from 2007 to 2008, 11,560 (93.1%) patients were followed up for 12 months. Their clinical characteristics and outcomes on death, recurrence, and dependency were recorded. The multivariate logistic regression was performed to determine whether there were gender differences in these outcomes. Women were older than men at baseline (67.9 vs. 64.0 years, P<0.001). Women had a higher mortality, recurrence rate, and dependency rate at 3, 6, and 12 months than men, but after adjusting for age, history of diabetes, pre-stroke dependency, stroke severity, in-hospital complications, and other confounders, there were no statistically significant differences in gender on mortality and recurrence rate at 3, 6, and 12 months; and dependency rate at 3, and 6 months. However, the dependency rate at 12 months remained significantly higher in women (odds ratio, 1.24; 95% confidence interval, 1.06 to 1.45).

Conclusions

There are many differences in clinical characteristics between women and men after ischemic stroke in China. Compared with men, women are more dependent at 12 months after stroke. This difference still exists after controlling the potential confounders.     

Observations on Anticoagulant Therapy in Thromboembolic Disease of the Brain

According to a recently reported study, anticoagulant therapy appears to be ineffective in thrombotic cerebrovascular disease when viewed from the standpoint of mortality, although it does control thrombosis in animals, recurrent ischemic attacks and progression of infarction in patients with stuttering strokes. The efficacy of anticoagulant therapy in preventing a catastrophic stroke is analyzed in the present report. Of 92 untreated patients followed up for an average period of 36 months, 28 suffered a recurrent stroke, only two of these being trivial. One trivial and 12 catastrophic strokes occurred in the first 16 months. Of 103 patients treated with anticoagulants for an average period of 16 months, seven had recurrent strokes, but five of these were trivial. In the first 16 months one catastrophic and four trivial strokes occurred. Anticoagulant therapy appears to be useful in preventing catastrophic strokes in selected patients in whom the risk of recurrent strokes justifies the risks involved in this treatment.     

Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution

BACKGROUND: An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. METHODS: Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. RESULTS: Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. CONCLUSIONS: Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.     

Multiscale Entropy of the Heart Rate Variability for the Prediction of an Ischemic Stroke in Patients with Permanent Atrial Fibrillation

Background

Atrial fibrillation (AF) is a significant risk factor for ischemic strokes, and making a robust risk stratification scheme would be important. Few studies have examined whether nonlinear dynamics of the heart rate could predict ischemic strokes in AF. We examined whether a novel complexity measurement of the heart rate variability called multiscale entropy (MSE) was a useful risk stratification measure of ischemic strokes in patients with permanent AF.

Methods and Results

We examined 173 consecutive patients (age 69±11 years) with permanent AF who underwent 24-hour Holter electrocardiography from April 2005 to December 2006. We assessed several frequency ranges of the MSE and CHA₂DS₂-VASc score (1 point for congestive heart failure, hypertension, diabetes, vascular disease, an age 65 to 74 years, and a female sex and 2 points for an age≥75 years and a stroke or transient ischemic attack). We found 22 (13%) incident ischemic strokes during a mean follow up of 3.8-years. The average value of the MSE in the very-low frequency subrange (90–300 s, MeanEn_VLF2) was significantly higher in patients who developed ischemic strokes than in those who did not (0.68±0.15 vs. 0.60±0.14, P<0.01). There was no significant difference in the C-statistic between the CHA₂DS₂-VASc score and MeanEn_VLF2 (0.56; 95% confidence interval, 0.43–0.69 vs. 0.66; 95% confidence interval, 0.53–0.79). After an adjustment for the age, CHA₂DS₂-VASc score, and antithrombotic agent, a Cox hazard regression model revealed that the MeanEn_VLF2 was an independent predictor of an ischemic stroke (hazard ratio per 1-SD increment, 1.80; 95% confidence interval, 1.17–2.07, P<0.01).

Conclusion

The MeanEn_VLF2 in 24-hour Holter electrocardiography is a useful risk stratification measure of ischemic strokes during the long-term follow-up in patients with permanent AF.     

Diffuse optical detection of global cerebral ischemia in an adult porcine model

Rapid screening for ischemic strokes in prehospital settings may improve patient outcomes by allowing early deployment of vascular recanalization therapies. However, there are no low-cost and convenient methods that can assess ischemic strokes in such a setting. Diffuse correlation spectroscopy (DCS) is a promising method for continuous, noninvasive transcranial monitoring of cerebral blood flow. In this study, we used a DCS system to detect cerebral hemodynamics before and after acute ischemic stroke in pigs. Seven adult porcines were chosen to establish ischemic stroke models via bilateral common carotid artery ligation (n = 5) or air emboli (n = 2). The results showed a significant difference in blood flow index (BFI) between the normal and ischemic groups. Relative blood flow index (rBFI) exhibited excellent results. Therefore, the diffuse optical method can assess the hemodynamic changes in acute cerebral ischemic stroke onset in pigs, and rBFI may be a promising biomarker for identifying cerebral ischemic stroke.     

The Neuroprotective Roles of Sonic Hedgehog Signaling Pathway in Ischemic Stroke

Ischemic stroke is characterized by high morbidity, mortality and disability rate worldwide. Because of its complexity in pathogenesis and lack of effective therapeutic strategies and drugs, great breakthrough has not yet been made in the treatment of cerebral ischemic stroke. Therefore, to explore a more effective and safer therapeutic strategy for cerebral ischemic stroke has been the focus of numerous researchers. Neuroprotective effects of sonic hedgehog (Shh) signaling pathway in ischemic stroke have been reported in recent studies, but have not been fully elucidated. In our review, we elaborate the roles of Shh signaling in ischemic stroke from different aspects, including oxidative stress, excitotoxicity, neuroinflammation, apoptosis, angiogenesis, neuroplasticity, neurogenesis, astrogliosis and oligodendrogenesis. Meanwhile, Shh signaling based therapeutic approaches for cerebral ischemic stroke are also included in our review. We hope it will benefit the readers to better understand the roles of Shh signaling pathway in cerebral ischemic stroke and provide more comprehensive insights for basic research and novel strategies for the clinical treatment of cerebral ischemic stroke.     

Effects of Body Mass Index on Risks for Ischemic Stroke,Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background

Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial.

Objective

This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients.

Methods

Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality).

Results

A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m²) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m²), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m²), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05).

Conclusions

Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.     

Depressive Symptoms and the Risk of Ischemic Stroke in the Elderly—Influence of Age and Sex

Although a relationship between depression and cardiovascular events has been suggested, past study results regarding the risk of stroke in relation to depression by subgroups are ambiguous. The aim of this study was to investigate the influence of depressive symptoms on risk of incident ischemic stroke in elderly according to age and sex. This prospective cohort study followed up 3852 subjects older than 55 years. Baseline depressive symptoms were defined by a score ≥5 on the Geriatric Depression Scale or antidepressant intake. The outcome measure was incident ischemic stroke within 6 years of follow-up. Multivariate Cox-proportional hazard models as well as cumulative survival analyses were computed. A total of 156 ischemic strokes occurred during the study period (24 strokes in the age-group<65 years and 132 strokes in the age-group≥65 years). The distribution of strokes in sex-subgroups was 4.5% in men and 3.7% in women. The multivariate analysis showed an elevated stroke risk (Hazard Ratio (HR): 2.84, 95% CI 1.11–7.29, p = 0.030) in subjects from 55 to 64 years with depressive symptoms at baseline but not in subjects older than 65 years. In the multivariate analysis according to sex the risk was increased in women (HR: 1.62, 95% CI 1.02–2.57, P = 0.043) but not in men. The Cox-regression model for interaction showed a significant interaction between age and sex (HR: 3.24, 95% CI 1.21–8.69, P = 0.020). This study corroborates that depressive symptoms pose an important risk for ischemic stroke, which is particularly remarkable in women and patients younger than 65 years.     

Craniectomy for malignant cerebral infarction: prevalence and outcomes in US hospitals

Object

Randomized trials have demonstrated the efficacy of craniectomy for the treatment of malignant cerebral edema following ischemic stroke. We sought to determine the prevalence and outcomes related to this by using a national database.

Methods

Patient discharges with ischemic stroke as the primary diagnosis undergoing craniectomy were queried from the US Nationwide Inpatient Sample from 1999 to 2008. A subpopulation of patients was identified that underwent thrombolysis. Two primary end points were examined: in-hospital mortality and discharge to home/routine care. To facilitate interpretations, adjusted prevalence was calculated from the overall prevalence and two age-specific logistic regression models. The predictive margin was then generated using a multivariate logistic regression model to estimate the probability of in-hospital mortality after adjustment for admission type, admission source, length of stay, total hospital charges, chronic comorbidities, and medical complications.

Results

After excluding 71,996 patients with the diagnosis of intracranial hemorrhage and posterior intracranial circulation occlusion, we identified 4,248,955 adult hospitalizations with ischemic stroke as a primary diagnosis. The estimated rates of hospitalizations in craniectomy per 10,000 hospitalizations with ischemic stroke increased from 3.9 in 1999–2000 to 14.46 in 2007–2008 (p for linear trend<0.001). Patients 60+ years of age had in-hospital mortality of 44% while the 18–59 year old group was found to be 24%(p = 0.14). Outcomes were comparable if recombinant tissue plasminogen activator had been administered.

Conclusions

Craniectomy is being increasingly performed for malignant cerebral edema following large territory cerebral ischemia. We suspect that the increase in the annual incidence of DC for malignant cerebral edema is directly related to the expanding collection of evidence in randomized trials that the operation is efficacious when performed in the correct patient population. In hospital mortality is high for all patients undergoing this procedure.     

An analysis of Methylenetetrahydrofolate reductase and Glutathione S-transferase omega-1 genes as modifiers of the cerebral response to ischemia

Background

Cerebral ischemia involves a series of reactions which ultimately influence the final volume of a brain infarction. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of the cerebral response to ischemia and impact the resultant stroke volume. The final volume of a cerebral infarct is important as it correlates with the morbidity and mortality associated with non-lacunar ischemic strokes.

Methods

The proteins encoded by the methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase omega-1 (GSTO-1) genes are, through oxidative mechanisms, key participants in the cerebral response to ischemia. On the basis of these biological activities, they were selected as candidate genes for further investigation. We analyzed the C677T polymorphism in the MTHFR gene and the C419A polymorphism in the GSTO-1 gene in 128 patients with non-lacunar ischemic strokes.

Results

We found no significant association of either the MTHFR (p = 0.72) or GSTO-1 (p = 0.58) polymorphisms with cerebral infarct volume.

Conclusion

Our study shows no major gene effect of either the MTHFR or GSTO-1 genes as a modifier of ischemic stroke volume. However, given the relatively small sample size, a minor gene effect is not excluded by this investigation.     

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke

Background

Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.

Methods

We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.

Results

Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.

Conclusion

Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.     

Effect of statins in stroke prevention

PURPOSE OF REVIEW: This paper reviews recent studies into the outcomes of clinical trials in which statin therapy has been used in the prevention and treatment of strokes. RECENT DEVELOPMENTS: Epidemiologic studies found no or little association between blood cholesterol levels and stroke. Randomized trials have confirmed that LDL lowering decreased the risk of stroke, in diabetic or hypertensive patients with 'normal' LDL cholesterol at baseline, and in patients with coronary artery disease, with respectively 48, 27 and 25% reduction in stroke incidence. A meta-analysis of trials showed that the greater the LDL cholesterol reduction, the greater the intima-media thickness and stroke risk reductions. Even if statins also have 'pleiotropic' effects, their main action seems to be through LDL reduction. The Heart Protection Study only included strokes that occurred 4.6 years before--a time when the stroke event rate is low and the cardiac event rate is high, and so may not have had the power to find a true effect of LDL cholesterol lowering in preventing recurrent stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial may give a definite answer because SPARCL investigators included 4732 patients with brain infarction or transient ischemic attacks and no history of myocardial infarction within 6 months of their stroke event, at a time when the expected stroke rate is very high and the myocardial infarction rate is very low. The results should be announced by mid-2006. SUMMARY: The positive effect of statins on stroke observed in trials of patients with coronary heart disease depended mainly on between-group LDL reduction, but other mechanisms could be involved. Though effective in prevention of major coronary events after a first stroke, statins have not yet been proven effective in prevention of recurrent stroke.     

Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action for Herbal Medicines in Stroke Treatment and Prevention

Annually, tens of millions of first-ever strokes occur in the world; however, currently there is lack of effective and widely applicable pharmacological treatments for stroke patients. Herbal medicines, characterized as multi-constituent, multi-target and multi-effect, have been acknowledged with conspicuous effects in treating stroke, and attract extensive interest of researchers although the mechanism of action is yet unclear. In this work, we introduce an innovative systems-pharmacology method that combines pharmacokinetic prescreening, target fishing and network analysis to decipher the mechanisms of action of 10 herbal medicines like Salvia miltiorrhizae, Ginkgo biloba and Ephedrae herba which are efficient in stroke treatment and prevention. Our systematic analysis results display that, in these anti-stroke herbal medicines, 168 out of 1285 constituents with the favorable pharmacokinetic profiles might be implicated in stroke therapy, and the systematic use of these compounds probably acts through multiple mechanisms to synergistically benefit patients with stroke, which can roughly be classified as preventing ischemic inflammatory response, scavenging free radicals and inhibiting neuronal apoptosis against ischemic cerebral damage, as well as exhibiting lipid-lowering, anti-diabetic, anti-thrombotic and antiplatelet effects to decrease recurrent strokes. Relying on systems biology-based analysis, we speculate that herbal medicines, being characterized as the classical combination therapies, might be not only engaged in multiple mechanisms of action to synergistically improve the stroke outcomes, but also might be participated in reducing the risk factors for recurrent strokes.     

Mouse Model of Intraluminal MCAO: Cerebral Infarct Evaluation by Cresyl Violet Staining

Stroke is the third cause of mortality and the leading cause of disability in the World. Ischemic stroke accounts for approximately 80% of all strokes. However, the thrombolytic tissue plasminogen activator (tPA) is the only treatment of acute ischemic stroke that exists. This led researchers to develop several ischemic stroke models in a variety of species. Two major types of rodent models have been developed: models of global cerebral ischemia or focal cerebral ischemia. To mimic ischemic stroke in patients, in whom approximately 80% thrombotic or embolic strokes occur in the territory of the middle cerebral artery (MCA), the intraluminal middle cerebral artery occlusion (MCAO) model is quite relevant for stroke studies. This model was first developed in rats by Koizumi et al. in 1986 ¹. Because of the ease of genetic manipulation in mice, these models have also been developed in this species ^2-3.Herein, we present the transient MCA occlusion procedure in C57/Bl6 mice. Previous studies have reported that physical properties of the occluder such as tip diameter, length, shape, and flexibility are critical for the reproducibility of the infarct volume ⁴. Herein, a commercial silicon coated monofilaments (Doccol Corporation) have been used. Another great advantage is that this monofilament reduces the risk to induce subarachnoid hemorrhages. Using the Zeiss stereo-microscope Stemi 2000, the silicon coated monofilament was introduced into the internal carotid artery (ICA) via a cut in the external carotid artery (ECA) until the monofilament occludes the base of the MCA. Blood flow was restored 1 hour later by removal of the monofilament to mimic the restoration of blood flow after lysis of a thromboembolic clot in humans. The extent of cerebral infarct may be evaluated first by a neurologic score and by the measurement of the infarct volume. Ischemic mice were thus analyzed for their neurologic score at different post-reperfusion times. To evaluate the infarct volume, staining with 2,3,5-triphenyltetrazolium chloride (TTC) was usually performed. Herein, we used cresyl violet staining since it offers the opportunity to test many critical markers by immunohistochemistry. In this video, we report the MCAO procedure; neurological scores and the evaluation of the infarct volume by cresyl violet staining.