Cerebrovascular Research Articles

Long-term health effects of a third-generation waste-to-energy plant: the experience of Turin (Italy).

The long-term study on adverse health effects of the third-generation waste-to-energy (WTE) plant located in Turin, Italy, is part of a broader health surveillance system. We considered 369 236 subjects living in areas with different levels of emission fallout, as well as a control group, from 1 January 2014, until the end of the follow-up period. Hospital admissions for cardiac diseases (ICD-IX: 390-429), ischaemic heart diseases (ICD IX: 410-414), chronic heart failure (ICD IX: 428.0, 428.2, 428.9), cerebrovascular diseases (ICD IX: 430-438), acute respiratory diseases (ICD IX: 460-466, 480-487), and COPD (ICD IX: 490-492, 494, 496) were evaluated for the population considered. Cox models were used, considering individual characteristics and overall environmental exposure. We also considered all births (n = 8296) of women residing in the area at the time of delivery during the study period. Log-binomial models were run separately for each outcome (sex ratio, multiple births, preterm births, on term low birthweight and small for gestational age births), adjusting for exposure to other pollution sources and maternal characteristics. Miscarriages were evaluated using hospital admissions registries. No relationship was found for the outcomes considered in the wider area, neither with hospital admissions nor with adverse reproductive outcomes. There is an association with chronic heart failure and ischaemic heart diseases in the maximum exposure area, but the small number of events suggests caution in interpreting this result. This study confirm results of other health surveillance lines, showing no evident harmful effects of the WTE plant.

Novel CT Image-Based Intracerebral Bleeding Risk Score for Patients With Acute Ischemic Stroke Undergoing Thrombolysis.

Symptomatic intracerebral hemorrhage (sICH) after intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke (AIS) remains a feared yet unpredictable complication. We aimed to develop and validate a new predictive model incorporating clinical variables and noncontrast head computed tomography imaging features to predict sICH in patients with AIS receiving intravenous recombinant tissue plasminogen activator. The predictive model was derived from 808 patients with AIS in the derivation cohort in Southeast China, based on multivariable logistic regression analysis. External validation was conducted in a validation cohort from Central China. Discrimination, calibration, and clinical usefulness of the predictive model were assessed. We observed 32 sICH events among 808 patients with AIS in the derivation cohort, and 21 sICH events out of 612 participants in the validation cohort. The variables in the predictive model included cerebral small vessel disease burden and early infarct signs on head computed tomography scan, atrial fibrillation, age, systolic blood pressure, and initial National Institutes of Health Stroke Scale score. The fitted model showed promising discrimination (optimism-corrected C statistic of 0.80) and acceptable calibration (Hosmer and Lemeshow goodness of fit P=0.816) in the derivation cohort. External validation showed similar discrimination (C statistic 0.82 [95% CI, 0.72-0.91]) and calibration (Hosmer and Lemeshow goodness of fit P=0.866). Our internally and externally validated prediction model for sICH in patients with AIS who received intravenous thrombolysis may facilitate individualized prediction for intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke.

Assessment of stress hyperglycemia ratio to predict all-cause mortality in patients with critical cerebrovascular disease: a retrospective cohort study from the MIMIC-IV database

BackgroundThe association between the stress hyperglycemia ratio (SHR), which represents the degree of acute stress hyperglycemic status, and the risk of mortality in cerebrovascular disease patients in the intensive care unit (ICU) remains unclear. This study aims to investigate the predictive ability of SHR for in-hospital mortality in critically ill cerebrovascular disease patients and to assess its potential to enhance existing predictive models.MethodsWe extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) database for patients diagnosed with cerebrovascular disease and used Cox regression to assess the association between SHR and mortality. To investigate the nature of this association, we applied restricted cubic spline analysis to determine if it is linear. The predictive ability of SHR for mortality risk was evaluated using receiver operating characteristic (ROC) curves and the C-index.ResultsWe included a total of 2,461 patients, with a mean age of 70.55 ± 14.59 years, and 1,221 (49.61%) being female. Cox regression analysis revealed that SHR was independently associated with both in-hospital mortality (per standard deviation (SD) increase: hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.23–1.48) and ICU mortality (per SD increase: HR 1.37, 95% CI 1.21–1.54). The risk of death increased in an approximately linear fashion when SHR exceeded 0.77–0.79. Subgroup analysis indicated the association was more pronounced in non-diabetic individuals. Additionally, incorporating SHR into existing models improved both discrimination and reclassification performance.ConclusionSHR serves as an independent risk factor for in-hospital mortality in cerebrovascular disease patients in the ICU. Adding SHR to existing models enhances their predictive performance, offering clinical value in the identification of high-risk patients.

Association between carotid artery hemodynamics and neurovascular coupling in cerebral small vessel disease: an exploratory study

Association between carotid artery hemodynamics and neurovascular coupling in cerebral small vessel disease: an exploratory study

The relationship between oxLDL, sLOX-1, PCSK9 and carotid intima-media thickness in patients with prediabetes and type 2 diabetes

Affection of vascular structures is a known complication in diabetes and prediabetes. Subclinical atherosclerosis begins to develop years before both cardiovascular and cerebrovascular diseases become symptomatic. The aim of this study was to evaluate the relationship between circulating oxidized LDL (oxLDL), soluble lectin-like oxidized LDL (sLOX)-1 and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and carotid intima-media thickness (CIMT) in patients with prediabetes and T2DM. We recruited 50 T2DM patients with macrovascular complications, 50 T2DM patients with uncomplicated, 50 prediabetes patients, and 50 healthy participants. The common carotid arteries were visualized by high-resolution B-mode carotid artery ultrasonography. Measurement of serum oxLDL, sLOX-1 and PCSK9 levels were assessed by using a commercially available human enzyme-linked immunosorbent assay (ELISA) method. Homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated. Circulating LDL-C, oxLDL, sLOX-1 and PCSK9 levels were significantly higher in T2DM patients with macrovascular complications compared to control group, prediabetes and uncomplicated diabetes. There was significant difference, especially between the controls and the T2DM patients with macrovascular complications. The CIMT increased progressively from control through to T2DM. Both right and left CIMT also showed significant differences between the groups of prediabetes versus uncomplicated diabetes at p < 0.001 showing progressive increase in vascular involvement with progression of disease. There was a positive correlation between PCSK9 levels with LDL-C, oxLDL, sLOX-1, and CIMT. ROC curve analyses showed that PCSK9, as well as oxLDL and LOX-1, was a strong predictor of T2DM with high sensitivity and specificity. In this study, we found that oxLDL, sLOX-1 and PCSK9 levels were significantly associated with carotid intima-media thickness. Our findings suggest that these biomarkers may be used as potential markers for the assessment of cardiovascular risk in patients with prediabetes and type 2 diabetes.

A database of magnetic resonance imaging-transcranial ultrasound co-registration.

As a portable and cost-effective imaging modality with better accessibility than Magnetic Resonance Imaging (MRI), transcranial sonography (TCS) has demonstrated its flexibility and potential utility in various clinical diagnostic applications, including Parkinson's disease and cerebrovascular conditions. To better understand the information in TCS for data analysis and acquisition, MRI can provide guidance for efficient imaging with neuronavigation systems and the confirmation of disease-related abnormality. In these cases, MRI-TCS co-registration is crucial, but relevant public databases are scarce to help develop the related algorithms and softwaresystems. This dataset comprises manually registered MRI and transcranial ultrasound volumes from eight healthy subjects. Three raters manually registered each subject's scans, based on visual inspection of image feature correspondence. Average transformation matrices were computed from all raters' alignments for each subject. Inter- and intra-rater variability in the transformations conducted by raters are presented to validate the accuracy and consistency of manual registration. In addition, a population-averaged MRI brain vascular atlas is provided to facilitate the development of computer-assisted TCS acquisitionsoftware. The dataset is provided in both NIFTI and MINC formats and is publicly available on the OSF data repository: https://osf.io/zdcjb/. This dataset provides the first public resource for the development and assessment of MRI-TCS registration with manual ground truths, as well as resources for establishing neuronavigation software in data acquisition and analysis of TCS. These technical advancements could greatly boost TCS as an imaging tool for clinical applications in the diagnosis of neurological conditions such as Parkinson's disease and cerebrovasculardisorders.

Mortality in Colombia due to cerebrovascular disease compared to coronary ischemic disease: 1995-2020

Mortality in Colombia due to cerebrovascular disease compared to coronary ischemic disease: 1995-2020

MT2A promotes angiogenesis in chronically ischemic brains through a copper–mitochondria regulatory mechanism

BackgroundApproximately half of patients with chronic ischemic cerebrovascular disease (CICD) exhibit poor revascularization. Metallothionein 2 A (MT2A) has a high affinity for metal ions and is potentially capable of chelating toxic copper ions to alleviate the impairment of angiogenesis. Therefore, we hypothesized that MT2A could promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions during copper overload (CPO).MethodsWe first collected dura matter (DM) samples from CICD patients and examined the expression of cuproptosis-related genes (DLAT, FDX1, and SDHB) to confirm the inhibitory effect of CPO on angiogenesis. Then, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of elesclomol and CuCl2 to determine the optimal concentration for inducing CPO. HUVEC activity and mitochondrial structure and function were detected to explore the ability of MT2A to alleviate CPO-induced damage. Finally, a rat model of 2-vessel occlusion plus encephalo-myo-synangiosis (2VO + EMS) with CPO was established to test the proangiogenic effect of MT2A through the copper–mitochondria regulatory mechanism in chronically ischemic brains.ResultsCompared with those from Matsushima grade A patients, DM samples from Matsushima grade C patients presented significantly greater DLAT and FDX1 expression and significantly lower SDHB expression. The optimal drug concentration for inducing CPO was subsequently determined, and in vitro experiments revealed that HUVEC activity was significantly decreased in the CPO group under hypoxic culture, accompanied by increased DLAT oligomerization, decreased SDHB expression, increased HSP70 expression. Moreover, significantly more common mitochondrial aberrations and significantly lower mitochondrial activity were detected in the CPO group compare with the control group. Additionally, MT2A overexpression alleviated CPO-induced mitochondrial dysfunction and cytotoxicity, improving HUVEC viability. In vivo, a CPO rat model was established, and CPO inhibited cerebral angiogenesis in 2VO + EMS model rats. Moreover, significantly greater CD31 expression, less DLAT accumulation, more mitochondria, and fewer mitochondrial abnormalities were observed in the CPOMT2A+ group than in the CPO group, accompanied by significantly improved cerebral blood perfusion and cognitive function.ConclusionMT2A can promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions and rescuing CPO-induced mitochondrial dysfunction.

Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease

Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease

Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults.

There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood-brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (kw)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A subsample had neuroimaging data including diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) for assessment of BBB kw and T2-weighted fluid-attenuated inversion recovery (FLAIR) for quantification of WMHs. Results indicated that higher plasma S100B levels were associated with poorer episodic memory performance (β = - .031, SE = .008, p < .001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB kw (interaction β = .095, SE = .042, p = .028) and between plasma S100B levels and deep WMH volume (interaction β = - .025, SE = .009, p = .007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB kw in the parietal lobe or increased deep WMH burden. Taken together, our results provide support for the combined use of biofluid and neuroimaging markers in the study of VCID.

Outcomes of type A aortic dissection in Australia.

Without surgical intervention, type A aortic dissection (TAAD) carries a high risk of life-threatening complications and mortality. Due to the low incidence of aortic dissection, case numbers vary significantly between institutions. This study reports outcomes for patients undergoing surgical TAAD repair in Australia between 2001 and 2021, and the impact of institution case numbers on mortality. Retrospective multicentre cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) data, including consecutive adult patients undergoing surgery for TAAD. Patients were divided into groups based on 30-day mortality. Secondary morbidity outcomes are reported. Between 2001 and 2021, 2604 patients (median age 65; 67% male) underwent operative intervention for TAAD. Over this period, the number of aortic dissections recorded in the database annually increased (from <50 to >200 cases per year), consistent with the increasing number of contributing institutions. Thirty-day mortality rates varied by unit from 0% to 100%, with an average over the period of 18%. Despite unit case numbers ranging from 1 or 2 to over 200 cases, funnel plot analysis demonstrated no units fell outside the accepted 99.7% control level for 30-day mortality. Individual surgeons showed decreased mortality with increased caseload. Non-survivors were more likely to have prior respiratory or cerebrovascular disease, previous myocardial infarction, or severe left ventricular dysfunction. Post-operative stroke, return to theatre for bleeding, renal failure and atrial fibrillation were more common in the non-survivors (P < 0.05). Mortality outcomes for TAAD in Australia have improved over time, stabilizing at 18% over the last 5 years. Units performing fewer operations for TAAD showed equivalent mortality outcomes to high volume units, while surgeons performing fewer procedures displayed a higher mortality.

Vasorelaxant effects and its mechanisms of the rhizome of Acorus gramineus on isolated rat thoracic aorta

In conventional medicine, the rhizome of Acorus gramineus Solander (AGR) is used to treat cardiovascular and cerebrovascular diseases. Decoctions containing AGR exert vasorelaxant effects. Therefore, this research aimed to delve deeper into the vasorelaxant effects and underlying mechanisms of AGR and its constituents (α-asarone and β-asarone). We assessed the vasorelaxant effect of a 50% ethanol extract of AGR (AGRE) using aortic rings from Sprague–Dawley rats pre-constricted with phenylephrine (PE) and potassium chloride (KCl). The findings suggested that the mechanism of this effect was independent of endothelial cells and was associated with vascular smooth muscle cells (VSMC). Since vasodilatory mechanisms associated with VSMC are predominantly influenced by K+ and Ca2+ channels, we explored various channels, including calcium-activated K+, voltage-dependent (delayed rectifier) K+, ATP-sensitive K+, inwardly rectifying K+, receptor-operated Ca2+ (ROCC), and voltage-dependent Ca2+ channels (VDCC). Selective blockers were used to examine K+ channels, which inhibited vasorelaxant effect of AGRE. These findings suggest that AGRE-induced vasorelaxation is facilitated through K+ channels. In addition, the blockage of Ca2+ influx was observed in both groups treated with PE and KCl. Therefore, AGR appears to block Ca2+ influx through ROCC and VDCC. In conclusion, AGR demonstrates vasorelaxant effects by acting on VSMC.

Correlation between blood pressure control status and cognitive impairment in older adults: A national cross-sectional study.

Hypertension is closely related to cognitive impairment; however, the correlation between blood pressure control and cognitive impairment in the hypertensive population is unclear. We aimed to explore the relationship between blood pressure control and cognitive impairment in older adults with hypertension. Using the cross-sectional data from the 2018 Chinese Longitudinal Healthy Longevity Survey, 5,860 people with self-reported history of hypertension were divided into the hypotension, intermediate blood pressure, and hypertension groups. Cognitive impairment was defined as a score of < 18 on the Chinese version of the Mini-Mental State Examination. Demographics of the population were also collected. Bivariate Logistic regression analysis and restricted cubic spline (RCS) model were used to analyze the relationship between blood pressure control and cognitive impairment. After adjusting for confounding factors, binary logistic regression analysis showed that the intermediate group was significantly associated with an increased risk of cognitive impairment than the hypotension group, whereas the hypertension group was significantly correlated with a reduced risk of cognitive impairment. No significant correlation was found between blood pressure control and cognitive impairment in patients aged <80 years, with hearing impairment, or with cerebrovascular diseases, whether in the hypotension or hypertension groups. There was a significant correlation between hypotension and cognitive impairment, and no correlation between hypertension and cognitive impairment in people aged ≥ 80 years, Han ethnicity and those who used antihypertensive drugs. Furthermore, RCS model analysis showed that there was a non-linear relationship between systolic blood pressure and cognitive impairment in individuals aged ≥ 80 years and those using antihypertensive drugs. There was a linear relationship between diastolic blood pressure and cognitive impairment. Blood pressure control in the hypertensive group was significantly associated with a lower risk of cognitive impairment.

Etiological Evaluation of Hyponatremia in Adult Patients Admitted into a Tertiary Care Hospital in Bangladesh

Hyponatremia, characterized by low sodium levels in the blood, is indeed a common electrolyte disorder, particularly among hospitalized patients. The clinical diagnosis can be challenging due to the varied symptoms it presents, and its etiology can be diverse. A cross-sectional, observational study was conducted in the Department of Medicine, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh, from September 2016 to March 2017, to evaluate the causes behind hyponatremia in adult patients. A total of 50 patients presented with clinical features and investigation-proven hyponatremia enrolled in this study as the study population purposively. Data was collected in pre-designed data collection sheet. Data compilation, sorting and analysis were conducted using the MS-Excel &amp; SPSS version 22.0. The majority of patients experienced multifactorial etiology for hyponatremia. The most prevalent cause was gastrointestinal loss (20%), followed by chronic renal insufficiency (16%), congestive cardiac failure (12%), cerebrovascular disease (10%), cirrhosis of the liver (10%), meningitis (6%), and thiazide diuretics (6%). Bronchogenic carcinoma and hypothyroidism were identified as the least common contributors to hyponatremia. Our study revealed a statistically significant difference between male and female participants in gastroenteritis causing hyponatremia (p=0.031). Gastrointestinal loss (gastroenteritis), cirrhosis of the liver, and bronchogenic carcinoma were predominant causes in the male population, accounting for 21.2%, 12.1%, and 6.07% respectively. In contrast, chronic renal insufficiency, hypothyroidism, and meningitis were important causes of hyponatremia in the female population, present in 17.6%, 11.7%, and 11.7% respectively. Recognizing the risk factors associated with symptomatic hyponatremia is crucial for devising effective preventive strategies. Mugda Med Coll J. 2024; 7(2): 77-81

Effectiveness of aspirin in preventing deep vein thrombosis following proximal femoral fracture surgery in Japan

Previous studies have shown that aspirin is effective as a prophylactic agent against venous thromboembolism (VTE) following proximal femoral fractures (PFF). In Japan, there is a lack of evidence regarding its efficacy and safety in this context. Consequently, aspirin is not covered by insurance for the prevention of venous thrombosis. This study aimed to investigate whether continued aspirin use in patients with PFF, who were already taking aspirin for cerebrovascular disease prevention before injury is effective as a prophylaxis for deep vein thrombosis (DVT). We retrospectively analyzed PFF patients (≥ 65 years) who underwent postoperative duplex ultrasonography from January 2010 to December 2023.The study compared patients taking aspirin alone (aspirin group) and those not taking antiplatelet agents or anticoagulants (control group), matched by propensity scores. We enrolled 1064 patients while 161 (15%) were in the aspirin group. After matching, 128 patients were analyzed. DVT incidence was not statistically significant between the aspirin (54) and control groups (60) (OR: 0.81; 95%CI: 0.49- 1.36; p = 0.44). Proximal DVT incidence was also similar (OR: 2; 95%CI: 0.50–7.00; p = 0.33). Additionally, since use of other postoperative antithrombotic prophylaxis (78%) is thought to have a significant impact on the incidence of DVT, a subgroup analysis was conducted to evaluate the effect of aspirin in patients who did not receive postoperative antithrombotic prophylaxis. Similarly, there was no statistically significant difference in either DVT (OR: 1.38; 95% CI: 0.55–3.42; p = 0.49) or proximal DVT (OR: 2.00; 95% CI: 0.37–10.92; p = 0.42). This study demonstrates that aspirin is not effective for preventing VTE in patients with PFF in Japan.

Augmented reality as a method of neuronavigation in microsurgical treatment of cerebrovascular diseases: description of the method and clinical experience

To describe AR-assisted neuronavigation in microsurgical treatment of intracranial aneurysms, arteriovenous malformations and cavernomas; to evaluate accuracy and applicability of AR-assisted neuronavigation. The study involved 22 patients with cerebral aneurysms, arteriovenous and cavernous malformations. Microsoft Hololens 2 HMD glasses and «Medgital» software for AR navigation were used. Accuracy of registration (TRE and FRE) and time for preoperative preparation were evaluated. TRE when using QR code was 0.6±0.2 cm, when combining through craniometric points - 1.4±0.6 cm. Time for preoperative image processing was 24.7±5.1 minutes, application setup in the operating theatre - 1.6±0.2 minutes. Combination using QR code provided higher accuracy of registration compared to craniometric points. AR-assisted navigation improved visualization and planning of surgeries for aneurysms, arteriovenous malformations, microvascular anastomoses and cavernous angiomas. AR-assisted navigation is an innovative method with specific advantages that can potentially improve microsurgical treatment of cerebrovascular diseases. Further research is needed to confirm these findings and develop AR technology in neurosurgery.

Association between Cerebral Small Vessel Disease and Periodic Limb Movements of Sleep in Stroke/TIA Patients.

Periodic limb movements (PLMs) of sleep, which may be linked to increased vascular events via nighttime sympathetic overactivity, have shown associations with cerebral small vessel disease (CSVD) in small studies. This study examined the relationship between PLMs and CSVD in a larger cohort, accounting for comorbidities. Patients with first-ever stroke or transient ischemic attack (TIA) were retrospectively analyzed. Polysomnography assessed the PLM index (PLMI) and PLM arousal index (PLMAI). CSVD was measured using radiographic markers, including the Fazekas score, total age-related white matter changes (ARWMC) score, microbleed counts, and lacunar infarcts. Multivariable regression models analyzed the association between an elevated PLMI and PLMAI with CSVD markers. This study included 86 patients (mean age 62.2±14.3 years, 66.3% male, mean BMI 28.1±5.7), 36 with a PLMI ≥5 (41.9%) and 11 with a PLMAI ≥5 (12.8%). Regression analyses showed that PLMI ≥5 and PLMAI ≥5 both predicted increased Fazekas and ARWMC total scores after adjusting for age, sex, BMI, and other comorbidities. Sensitivity analyses using age- and sex-specific PLMI cut-offs also showed that a PLMI exceeding the upper limit of normal predicted an increased Fazekas score and approached significance for the ARWMC score. PLMI was not significantly associated with cerebral microbleeds or lacunar infarcts. In patients with first-ever minor stroke and TIA, a significant association was observed between PLMI and PLMAI with white matter hyperintensities (WMHs) after adjusting for confounders. Future studies may help determine the directionality of this association and whether PLMs independently predict CSVD.

Infarct volume as a predictor and therapeutic target in post-stroke cognitive impairment

Post-stroke cognitive impairment is one of the most common consequences of stroke, affecting more than half of stroke patients, especially in the geriatric population. Post-ischemic stroke cognitive impairment (PISCI) is particularly detrimental, as it can exacerbate a patient’s disability. Given that the severe consequences of adverse life outcomes are major contributors to disability and death among survivors of ischemic stroke, preventing stroke and PISCI remains a fundamental strategy for maintaining optimal brain health. Recent studies have extensively investigated the epidemiology, diagnosis, and management of PISCI. Nevertheless, significant gaps persist in our understanding of its pathophysiological mechanisms and potential therapeutic targets, which warrants further research. Factors such as baseline brain health, cerebral small vessel disease, and stroke characteristics (e.g., infarct location, severity, and morphology) have been associated with PISCI. However, its pathophysiology remains inadequately understood. Recent research suggests that infarct volume may serve as a novel indicator for predicting and managing PISCI. Thus, this review aims to expand our understanding of factors influencing PISCI and to elucidate its pathophysiological mechanisms. In particular, infarct volume has been proposed as a potential target and may play a critical role in predicting and managing PISCI. We advocate for improved and timely predictions of PISCI to enhance the quality of life for patients and reduce the economic and emotional burden on caregivers.

Strengthening the Link Between Periodic Leg Movements during Sleep and Cerebral Small Vessel Disease.

Strengthening the Link Between Periodic Leg Movements during Sleep and Cerebral Small Vessel Disease.

Identification of a central regulator of ginkgolide biosynthesis in Ginkgo biloba that integrates jasmonate and light signaling

Ginkgolides are secondary metabolites unique to Ginkgo biloba with the potential to prevent and treat cardiovascular and cerebrovascular diseases. Although the biosynthetic pathways of ginkgolides have been partly uncovered, the mechanism regulating their biosynthesis is still largely unknown. Here, using multiomic and genetic analyses, we report the identification of a transcription factor, named ETHYLENE RESPONSE FACTOR ASSOCIATED WITH GINKGOLIDE BIOSYNTHESIS (GbEAG), as a critical regulator of ginkgolide biosynthesis. GbEAG is highly expressed in the roots of G. biloba, and its expression is significantly induced by methyl jasmonate (MeJA). Ginkgolide content was significantly increased in roots by overexpressing GbEAG using a "cut-dip-regeneration" system. GbEAG positively regulates ginkgolide biosynthesis by directly binding to the GCC-boxes in the promoter regions of genes involved in the biosynthesis of ginkgolides, such as ISOPENTENYL DIPHOSPHATE ISOMERASE (GbIDI) and CYTOCHROME P450 7005C3 (GbCYP7005C3). GbEAG mediates the jasmonic acid (JA)-activated ginkgolide synthesis through its direct interaction with the JASMONATE ZINC-FINGER INFLORESCENCE MERISTEM DOMAIN 3 (GbJAZ3) repressor. Importantly, we also found that the central light-response regulator ELONGATED HYPOCOTYL 5 (GbHY5) mediates light induction of ginkgolide biosynthesis by binding to the G-box in the GbEAG promoter. Our findings provide mechanistic insights into the coordinated regulation of ginkgolide biosynthesis via JA and light signals, with GbEAG as a central regulator in G. biloba, and shed light on the potential to develop ginkgolide-rich varieties through molecular breeding and gene editing.