Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response.

BACKGROUND: In traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO). METHODS: C57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000-3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining. RESULTS: Pretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response. CONCLUSIONS: This study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Integrative Approaches in Acute Ischemic Stroke: From Symptom Recognition to Future Innovations.

Among the high prevalence of cerebrovascular diseases nowadays, acute ischemic stroke stands out, representing a significant worldwide health issue with important socio-economic implications. Prompt diagnosis and intervention are important milestones for the management of this multifaceted pathology, making understanding the various stroke-onset symptoms crucial. A key role in acute ischemic stroke management is emphasizing the essential role of a multi-disciplinary team, therefore, increasing the efficiency of recognition and treatment. Neuroimaging and neuroradiology have evolved dramatically over the years, with multiple approaches that provide a higher understanding of the morphological aspects as well as timely recognition of cerebral artery occlusions for effective therapy planning. Regarding the treatment matter, the pharmacological approach, particularly fibrinolytic therapy, has its merits and challenges. Endovascular thrombectomy, a game-changer in stroke management, has witnessed significant advances, with technologies like stent retrievers and aspiration catheters playing pivotal roles. For select patients, combining pharmacological and endovascular strategies offers evidence-backed benefits. The aim of our comprehensive study on acute ischemic stroke is to efficiently compare the current therapies, recognize novel possibilities from the literature, and describe the state of the art in the interdisciplinary approach to acute ischemic stroke. As we aspire for holistic patient management, the emphasis is not just on medical intervention but also on physical therapy, mental health, and community engagement. The future holds promising innovations, with artificial intelligence poised to reshape stroke diagnostics and treatments. Bridging the gap between groundbreaking research and clinical practice remains a challenge, urging continuous collaboration and research.

Vitamin D and Restless Legs Syndrome: A Review of Current Literature.

This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vitamin D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interaction of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the paradoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care. Highlights  Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.

[Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease].

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides.

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.

Stachydrine, a potential drug for the treatment of cardiovascular system and central nervous system diseases.

Cardiovascular disease (CVD) is the leading cause of death globally and poses at significant challenge in terms of effective medical treatment. Leonurus japonicus Houtt, a traditional Chinese herb, is widely used in China for the treatment of obstetrical and gynecological disorders, including menstrual disorders, dysmenorrhea, amenorrhea, blood stasis, postpartum bleeding, and blood-related diseases such as CVD. Stachydrine, the main alkaloid component of Leonurus, has been shown to exhibit a wide range of biological activities including anti-inflammatory, antioxidant, anti-coagulant, anti-apoptotic, vasodilator, angiogenic promoter. Additionally, it has been demonstrated to have unique advantages in the prevention and treatment of CVD through regulation of various disease-related signaling pathways and molecular targets. In this comprehensive review, we examine the latest pharmacological effects and molecular mechanisms of Stachydrine in treating cardiovascular and cerebrovascular diseases. Our aim is to solid scientific basis for the development of new CVD drug formulations.

Treatment Patterns for Sickle Cell Disease among Those with Cerebrovascular Disease in the USA.

BACKGROUND: New treatments and guidelines in sickle cell disease (SCD) have improved the quality and lifespan of SCD patients. Over 90% of people with SCD will live into adulthood, and the majority will live past 50 years of age. However, data on comorbidities and treatments among SCD patients with and without cerebrovascular disease (CVD) are limited. OBJECTIVES: The objective of this study was to describe the outcomes and preventive treatments used on SCD patients with and without CVD, based on a dataset of over 11,000 SCD patients. METHODS: We identified SCD patients with and without CVD from the MarketScan administrative database using validated International Classification of Diseases, 10th Revision, Clinical Modification codes from January 1, 2016, to December 31, 2017. We summarized treatments received (iron chelation, blood transfusion, transcranial Doppler, and hydroxyurea) and tested for differences by CVD status using the t test for continuous variables and the χ2 for categorical variables. We also tested for differences among SCD, stratifying by age (<18 years vs. ≥18 years). RESULTS: Of the 11,441 SCD patients, 833 (7.3%) had CVD. SCD patients with CVD were more likely to have diabetes mellitus (32.4% among those with CVD vs. 13.8% without CVD), congestive heart failure (18.3 vs. 3.4%), hypertension (58.6 vs. 24.7%), chronic kidney disease (17.9 vs. 4.9%), and coronary artery disease (21.3 vs. 4.0%). SCD patients with CVD were more likely to receive a blood transfusion (15.3 vs. 7.2%) and hydroxyurea (10.5 vs. 5.6%). Fewer than 20 patients with SCD were given iron chelation therapy, and none received transcranial Doppler ultrasound. Hydroxyurea was prescribed among a greater percentage of children (32.9%) than adults (15.9%). CONCLUSIONS: There appears to be an underutilization overall of treatment options among SCD patients with CVD. Further research would confirm these trends and explore ways to increase utilization of standard treatments among SCD patients.

Risk Factors of Dementia in Patients with Cerebral Vascular Diseases Based on Taiwan National Health Insurance Data.

INTRODUCTION: Vascular factors have been shown to be associated with increased risk of dementia. However, clinical trials have so far been unsuccessful, suggesting new approaches are needed. The aim of this study was to use population-based real-world data to investigate risk factors and preventive factors for dementia, including the effects of traditional Chinese medicine (TCM). METHODS: This is a retrospective cohort study using LHID2000, a dataset randomly selected from Taiwan's National Health Insurance Research Database. Subjects with occlusion and stenosis of precerebral and cerebral arteries, cerebral atherosclerosis without mention of cerebral infarction, and transient cerebral ischemia were included. Subjects with dementia at baseline were excluded. The primary endpoint was dementia. Data for demographic and clinical comorbid status and treatments administered at baseline in 2000 and at the end of follow-up in 2013 were included. RESULTS: A total of 4,207 subjects with cerebral vascular disease and no cognitive impairment were included, of whom 392 converted to dementia during an average 5.15-year (SD: 3.79) follow-up. Depression (adjusted HR: 1.54, 95% confidence interval [CI]: 1.13-2.09), osteoporosis (adjusted HR: 1.34, 95% CI: 1.04-1.74), and the use of enalapril (adjusted HR: 1.37, 95% CI: 1.09-1.73) were risk factors for dementia, while nitroglycerin (adjusted HR: 0.67, 95% CI: 0.53-0.85) was a protecting factor, in subjects with cerebrovascular diseases without mention of cerebral infarction. In total, statins were shown to be associated with decreased risk of dementia (HR: 0.73, 95% CI: 0.59-0.91); however, no one statin subtype or TCM had such an effect. CONCLUSION: Depression, osteoporosis, and the use of enalapril were associated with a higher risk of dementia, while nitroglycerin might be a protecting factor for dementia, in subjects with cerebrovascular diseases without mention of cerebral infarction.

The effect of pelvic floor muscle training on urinary incontinence in patients with stroke: a systematic review and meta-analysis.

BACKGROUND: No other systematic review presented the effectiveness of pelvic floor muscle training (PFMT) in individual with stroke. AIMS: The purpose of this systematic review and meta-analysis was to demonstrate the effectiveness of PFMT for urinary incontinence in patients with stroke. METHODS: "Web of Science (WoS), Cochrane Library, PubMed and Scopus" databases were searched. "Revised Cochrane risk-of-bias tool randomized trials (RoB 2)" and "PEDro" were used to assess the risk of bias and methodological quality of the studies. Narrative synthesis and meta-analysis were conducted to present the results. RESULTS: A total of 8 articles were included in the review. Seven articles were classified as "good" level evidence. Four articles were considered to have "high risk" of bias for the overall score. Regarding two homogenous studies, PFMT-based rehabilitation was not superior standard urinary incontinence therapy on SF-36-Social Function score at 12-week follow-up (ES 0.47, 95% CI - 0.16-0.96). Data pooling of two studies did not provide an additional advantage of pelvic muscle training on 3 days voiding diary (night, total day) score at 12-week follow-up (ES 28, 95% CI - 0.61-0.48; ES 0.30, 95% CI - 0.23-0.95). On the other hand, low-quality evidence demonstrated that pelvic muscle training yielded better results on daytime voiding (ES 0.28, 95% CI 0.04-1.16). CONCLUSIONS: The results demonstrated that PFMT had positive effects in terms of daytime urination frequency and incontinence. Although some studies have reported positive effects on symptoms, function, strength, and endurance, the generalizability of these results is controversial. Further studies should assess the quality-of-life and function with urinary incontinence and stroke-specific tools.

Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease / 中国中药杂志

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats.

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men.

BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 µmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

Tetramethylpyrazine: A review on its mechanisms and functions.

Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.

[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Cerebrovascular disease at young age is related to mother's health during the pregnancy-The Northern Finland Birth Cohort 1966 study.

BACKGROUND AND PURPOSE: For prevention of cerebrovascular diseases at younger age, it is important to understand the risk factors occurring early in life. We investigated the relationship between mothers' general health during pregnancy and the offspring's risk of cerebrovascular disease in age of 15 to 52 years. METHODS: Within the population-based prospective Northern Finland Birth Cohort 1966, 11,926 persons were followed from antenatal period to 52 years of age. Information on their mother's ill health conditions, i.e., hospitalizations, chronic diseases, medications, vitamin or iron supplement, fever, anemia, mood, and smoking was collected from 24th gestational week onwards. Ischemic and hemorrhagic cerebrovascular diseases of the offspring were identified from national registers in Finland. Cox proportional hazard models were used to estimate the association of mother's health conditions with incidence of cerebrovascular disease in the offspring, with adjustments for potential confounders. RESULTS: During 565,585 person-years of follow-up, 449 (2.8%) of the offspring had a cerebrovascular disease. Hospitalization during pregnancy was associated with an increased risk of cerebrovascular disease in the offspring (hazard ratio (HR) = 1.49; 95% confidence interval (CI) 1.06-2.08) after adjustment for confounders, as was having more than three ill health conditions (HR = 1.89; CI 1.14-3.11). Not using vitamin or iron supplement was associated with increased risk for cerebrovascular disease in the offspring (HR = 1.39; CI 1.01-1.89). CONCLUSIONS: The results suggest that the risk of cerebrovascular disease may start as early as during the antenatal period, and the health characteristics of mothers during pregnancy may play a role in cerebrovascular disease risk of the offspring.

Quantitative analysis of effects of salvianic acid a combined with hydroxy safflower yellow a on rat endothelial cells after hypoxic injury using the combination index method

Abstract Cerebrovascular disease is the second most serious disease in the world. It has the features of high morbidity, high mortality and recurrence rate. Numerous research on the compatibility of Chinese medicine with effective ingredients of cerebral ischemia has been made during the past decades. The purpose of this study is to quantitatively analyze the combined pharmacological effect of effective ingredients in Danshen and Honghua (Dan Hong) on rat microvascular endothelial cells after gradually oxygen-glucose deprivation. The experimental concentration range for the compatibility of two effective ingredients were determined in the preliminary experiments by Cell Counting kit-8 (CCK-8) method. Drugs were added to rat brain microvascular endothelial cells at a non-toxic dose level. After that, the cells were cultured for 12 h, and placed in a hypoxic environment. Finally, the cell survival rate was used as a measure of drug effect. In order to determine synergism or antagonism, the combination index (CI)-isobologram method was performed to analyze the data from the experiments. Based on this theory, the potencies of each drug and the shapes of their does-effect curves are both taken into account. The results show that the synergism or the antagonism between two effective ingredients compatibility change with different proportion and dosage. Furthermore, it can be seen from the results of these experiments that when these drugs are used in combination, the dosage required to achieve the same therapeutic effects is greatly reduced compared with the case of single one. It is worth mentioning that our experiments also prove that the median-effect equation and the CI method can be applied in the field of traditional Chinese medicine.

[Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases].

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.

Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies.

BACKGROUND: Stroke is a crucial health threat to adults worldwide. Despite extensive knowledge of risk-factor mitigation, no primary prevention exists for healthy people. Coffee is a widely consumed beverage globally. Health benefit of coffee for several neurological diseases has been identified; however, the association between stroke risk and coffee consumption in healthy people has not been determined. We investigated the effect of coffee on stroke risk by conducting a meta-analysis of prospective cohort studies. METHODS: Electronic databases, namely PubMed, BioMed Central, Medline, and Google Scholar, were searched using terms related to stroke and coffee. Articles that described clear diagnostic criteria for stroke and details on coffee consumption were included. The reference lists of relevant articles were reviewed to identify eligible studies not shortlisted using these terms. Enrolled studies were grouped into three outcome categories: overall stroke, hemorrhagic stroke, and ischemic stroke. RESULTS: Seven studies were included and all of them were large-scale, long-term, follow-up cohort studies of a healthy population. Upon comparing the least-coffee-consuming groups from each study, the meta-analysis revealed a reduction in the risk of overall stroke during follow-up (hazard ratio [HR] for overall stroke = 0.922, 95% confidence interval [CI] = 0.855-0.994, P = 0.035). In studies with a clear definition of hemorrhagic and ischemic stroke, coffee consumption reduced the risk of ischemic stroke more robustly than that of hemorrhagic stroke (hemorrhagic, HR = 0.895, 95% CI = 0.824-0.972, P = .008; ischemic, HR = 0.834, 95% CI = 0.739-0.876, P < .001). No obvious dose-dependent or U-shaped effect was observed. CONCLUSIONS: Coffee consumption reduces the risk of overall stroke, especially ischemic stroke. Further investigation is required to identify beneficial components in coffee, including caffeine and phenolic acids, to develop preventive medication for stroke.