Cerebral small vessel disease (CSVD) is a major cause of lacunar stroke, vascular cognitive impairment, and gait disturbance, yet the development of disease-modifying therapies is limited by the lack of robust, non-invasive biomarkers of microvascular pathology. Arterial spin labeling (ASL) MRI enables quantitative, non-invasive, contrast-free measurement of cerebral blood flow (CBF) and is well suited for longitudinal studies. In routine clinical and research practice, single-delay three-dimensional pseudo-continuous ASL (pCASL) with an appropriately long post-labeling delay is the workhorse implementation and has already been applied in several CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and hereditary CSVD cohorts, while more advanced approaches such as multi-delay ASL and diffusion-prepared pCASL can additionally probe arterial transit time (ATT) and blood-brain barrier (BBB) water exchange. CADASIL, caused by pathogenic NOTCH3 variants, is a prototypical monogenic CSVD with relatively low etiologic heterogeneity, providing a powerful clinical model in which to study microvascular dysfunction and trial-ready imaging markers. In this review, we synthesize data on ASL in CADASIL, including relationships between CBF, cognition, and lesion burden, evidence from acute encephalopathic episodes, and emerging work on ATT and BBB water exchange. We further compare perfusion profiles across monogenic (HTRA1-related CSVD, Fabry disease) and sporadic CSVD, and discuss how ASL-derived measures-CBF, ATT, and BBB water exchange rate-can be incorporated as imaging endpoints in CADASIL therapeutic trials. In particular, standardized single-delay three-dimensional pCASL provides a practical, scalable method to quantify regional CBF as a primary perfusion endpoint.
Type 1 diabetes is a risk factor for retinal microvascular pathology, cerebral small vessel disease (cSVD), and cognitive deficits. In older individuals with type 1 diabetes, decreased vessel densities of superficial (SCP) and deep (DCP) retinal capillary plexuses have been associated with cognitive impairment. We assessed whether these associations are already evident in midlife among individuals without overt neurological symptoms. We also investigated whether cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), manifestations of cSVD, modify these associations. We measured vessel density of the SCP and DCP, and area of foveal avascular zone (FAZ) in macular 3×3 mm optical coherence tomography angiography (OCTA) images and performed a comprehensive neuropsychological assessment and brain MRI in 153 adults with type 1 diabetes (age 46.4±7.5 years, diabetes duration 30.7±10.1 years). In univariate analyses, SCP, DCP, and FAZ were related to measures of processing speed and executive functions (standardized β ranged from -0.29 to -0.19, p-values from <0.001 to 0.018). However, after adjusting for age and relevant clinical markers, only association between FAZ and a sensitive working memory task (standardized β=-0.25, p<0.05) remained significant. In interaction analyses, CMBs and WMHs did not modify these associations. Enlarged FAZ was associated with poorer working memory performance independently of confounding factors. Otherwise, age largely explained the associations between retinal microvascular structure and cognition in middle-aged individuals with type 1 diabetes without any overt neurological symptoms.
Cerebral microbleeds (CMBs) are observed in one-third of CADASIL patients and increase with age. Factors associated with CMBs vary across studies, likely due to inadequate handling of their zero-inflated, long-tailed distribution and lack of accounting for measurement variability. We aimed to assess these factors while addressing these limitations. CMBs were assessed in a large CADASIL cohort, with demographic, vascular, genetic, imaging, and clinical data. White matter hyperintensity volume (WMH), lacune count, and brain parenchymal fraction (BPF) were measured. A Hurdle model was used to distinguish factors associated with CMB presence from those related to lesion counts, while accounting for measurement variability. Three models were built with: (1) demographic/biological factors; (2) MRI markers; and (3) clinical variables. Beyond the consistent effect of the MRI sequence, in Model 1, CMB presence was associated with age, male sex and hypertension, while counts were associated only with age. In Model 2, CMB presence was associated with age, hypertension, and lacune count; counts were higher with WMH and antiplatelet use, and lower with EGFr 1-6 mutations and BPF. In Model 3, CMB presence was associated with age, hypertension, stroke history and gait disturbances; counts were associated with education, lacune count, MMSE ≤24, and hypercholesterolemia measured at the study visit. Hurdle modeling distinguishes determinants of CMB occurrence from accumulation. Hypertension appears to lower the threshold for lesion emergence along aging. CMB burden is associated with the burden of cerebrovascular lesions, brain atrophy and clinical severity, supporting worsening of the microangiopathic process, with specific impact related to mutation type.
There is increasing evidence of an inverse relationship between air pollution and cognitive functioning. Yet, the biological mechanisms underlying this relationship remain underexplored in healthy and vulnerable populations. This study examined cross-sectional and longitudinal associations between air pollution and global cognitive functioning in individuals without or with heart failure, carotid occlusive disease, or vascular cognitive impairment. We also assessed whether the cross-sectional associations were mediated by white matter hyperintensities (WMH), total brain volume (TBV), and cerebral blood flow (CBF). The cross-sectional and longitudinal analyses included data from 341 and 180 Heart-Brain Study participants, respectively. Cognitive functioning was measured using neuropsychological tests at baseline and two-year follow-up. Brain Magnetic Resonance Imaging provided WMH and TBV in mL, and CBF in mL/100g/min. WMH and TBV were divided by total intracranial volume. Annual average outdoor concentrations of particulate matter with diameters <2.5 µm and <10.0 µm, and nitrogen dioxide in µg/m3 in residential six-digit postal code areas were linked to participants at baseline. Adjusted multi-level regression analyses showed no significant cross-sectional or longitudinal associations between air pollution and global cognitive functioning. The associations between air pollutants and global cognitive functioning were not significantly mediated by WMH, TBV, and CBF. In this study, air pollution was not associated with global cognitive functioning or brain health indicators in healthy individuals and those with cardiovascular disorders along the heart-brain axis. Larger studies with longer follow-up periods are warranted to extend the present findings and to further elucidate potential associations between air pollution, cognition, and the underlying biological mechanisms.
Alzheimer's disease (AD) is the primary cause of dementia worldwide, imposing a substantial health and economic burden. In Vietnam, an aging population and rapid socioeconomic changes have intensified concerns about AD and other dementias burden. We analyzed data from the Global Burden of Disease (GBD) 2021 database to estimate age-standardized rates (ASRs) of incidence, prevalence, mortality, years lived with disability (YLDs), and years of life lost (YLLs) for AD in Vietnam from 1990 to 2021. Trends were assessed using Joinpoint regression, and risk factors were examined based on their contributions to disability-adjusted life years (DALYs) and mortality. Subgroup analysis by age and sex were also conducted. In 2021, the ASRs for AD and other dementias incidence and prevalence in Vietnam were 110.09 (95 % UI: 96.21-126.57) and 649.42 (95 % UI: 556.89-744.39) per 100,000 persons which were comparable to those in the Southeast Asia region and globally, with the burden predominantly observed in individuals aged 65 and older. Despite a declining trend in incidence and prevalence over the study period (AAPC -0.185 % and -0.199 %), both DALYs and mortality rates increased significantly (AAPC 0.155 % and 0.339 %). High fasting plasma glucose, elevated body mass index (BMI), and smoking emerged as the most significant risk factors. Despite a decline in incidence and prevalence from 1990 to 2021, rising DALYs and mortality rates highlight the growing burden of AD and other dementias in Vietnam. High fasting plasma glucose, elevated BMI, and smoking are important risk factors.
Cardiovascular (CV) risk factors are associated with cerebrovascular damage and cognitive decline in late-life. However, it is unknown how different ethnic CV risk profiles relate to cerebral haemodynamics in mid-life. We aimed to investigate associations of CV risk factors with cerebral haemodynamics at two timepoints and examine the impact of ethnicity on these measures. From the HELIUS study (53.0 years, 44.8 % female), participants of Dutch (n = 236), Moroccan (n = 122), or South-Asian Surinamese (n = 173) descent were included. Cerebral blood flow (CBF) and its spatial coefficient of variation (sCoV, an ASL-label arrival measure of macrovascular efficiency) were obtained in grey (GM) and white matter (WM). CV risk factors were assessed 8.4 years [7.4-9.5] (first visit) and 2.2 years [1.8-2.6] (second visit) prior to MRI. Associations of CV risk factors, WM hyperintensities (WMH), and carotid plaques with cerebral haemodynamics were investigated using linear regressions. CBF and sCoV differed per ethnicity. Only at the second visit associations were found, without an interaction with ethnicity; history of CV disease with lower GM CBF and higher WM sCoV, higher total cholesterol and lower WMH volume with lower WM CBF, smoking with higher WM sCoV, and higher SBP with lower GM sCoV. These findings suggest that cerebral haemodynamics differ between ethnic groups in midlife. Although no interaction with ethnicity was found in the associations of CV risk factors, the observed differences in CBF and sCoV highlight the need to further explore how ethnic-specific risk profiles may contribute to cerebrovascular pathology over time.
White matter hyperintensities (WMH) are a core marker of cerebral small vessel disease (CSVD), but their interpretation is limited by strong age-dependence. We hypothesized that WMH burden disproportionate to age- and sex-expected norms had clinical significance by reflecting disease burden and outcomes. We developed an age- and sex-referenced normative model of WMH using hierarchical Bayesian regression in 2544 neurologically healthy community-dwelling adults from Taiwan and Japan (50.0-92.1 years, 1319 women). Individualized WMH deviation scores were applied to 1237 community-dwelling participants. Participants were classified into four normative model-defined WMH deviation categories: low, mild, moderate, and high. We tested associations of WMH deviation with vascular risk profiles, cognitive performance, gray matter volumes, and all-cause mortality. Higher WMH deviation identified individuals who were not older but had more adverse vascular profiles. Each one-level increase in WMH deviation was associated with lower global cognition (MMSE β = -0.179, FDR-p = 0.034), poorer verbal memory (β = -0.121, FDR-p = 0.034), and worse visuospatial function (β = -0.330, FDR-p = 0.049), as well as reduced global gray matter (β = -4.180, FDR-p < 0.001) and lower hippocampal and thalamic volumes (all FDR-p ≤ 0.002). During a mean follow-up of 9.4 years, high WMH deviation was associated with increased all-cause mortality after adjustment for age, sex, hypertension, and diabetes (hazard ratio 1.72, 95% CI 1.05-2.82), despite younger age. WMH deviation from age- and sex-expected norms provides clinically-relevant information identifying individuals at increased risk of neurodegeneration and mortality.
Aging of the central nervous system is accompanied by a progressive decline in neuroplasticity, regenerative capacity, and vascular integrity. Neural stem cells (NSCs) and cerebral vasculature are both critically involved in maintaining homeostasis, and their age-related dysfunction contributes to neurodegenerative and cerebrovascular diseases. This article explores the mechanisms underlying NSC aging and vascular deterioration, their mutual interconnection, and the implications for brain health in aging populations. We review current evidence on molecular and cellular pathways affecting neurogenesis and cerebral perfusion, including dysregulation of BDNF, VEGF, mTOR, AMPK, and the effects of oxidative stress and chronic inflammation. We also highlight emerging biomarkers and therapeutic targets. Aging disrupts the neurovascular unit, impairing both neurogenesis and vascular support systems. Chronic inflammation and oxidative stress exacerbate these processes, forming a self-perpetuating degenerative cycle. Antioxidant and anti-inflammatory therapies, along with stem cell-based interventions such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), show promise for restoring neural and vascular function. Addressing both NSC and vascular aging is essential for developing effective interventions against cognitive decline and cerebrovascular pathology. Integrative and personalized therapeutic strategies targeting shared molecular pathways hold great promise for future clinical applications.
To determine the independent and joint associations of five markers of white matter integrity, including white matter hyperintensities (WMH), extracellular free water (FW), fractional anisotropy (FA), peak width of skeletonized mean diffusivity (PSMD), and Diffusion tensor image analysis along the perivascular space index (ALPS) on cognitive performance and its trajectory in cognitively diverse individuals. 574 participants from the University of California, Davis Alzheimer's Disease Research Center (UCD ADRC) longitudinal cohort, aged 77 ± 7 years received yearly comprehensive clinical evaluations and a baseline MRI exam. Baseline MRI measures, including WMH, FW, FA, PSMD, and ALPS, were computed for each individual and used as independent variables to explain baseline and change in episodic memory (EM) and executive function (EF) using linear regression with stepwise adjustment. Bayesian Model Averaging (BMA) was then applied to derive robust estimates of each marker's contribution to cognition and its longitudinal trajectory, accounting for their joint inclusion in the same model. Analyses showed that higher baseline WMH, FW, and PSMD, as well as lower FA and ALPS, were significantly associated with poorer cognitive performance (p < 0.05). These associations remained robust after adjusting for relevant covariates-including age, sex, education, hypertension, diabetes, and hippocampal volume-except for FA and ALPS, which were no longer associated with EM (p > 0.05). Higher baseline WMH, FW, and PSMD, and lower FA, were also significantly associated with annual decline in EF and EM, whereas ALPS showed no association with cognitive change (p > 0.05). After covariate adjustment, these associations remained significant, except for PSMD and FA which were no longer significantly associated with EM trajectory. Joint modeling using BMA identified FW and WMH as the most likely contributors to both baseline performance and change in EF and EM, with posterior inclusion probabilities exceeding 50 %. This study identified both cross-sectional and longitudinal associations between five markers of white matter integrity and cognitive performance and decline. Using BMA-a method designed to disentangle the specific contribution of each marker while accounting for multicollinearity-we found that, among the five markers, FW and WMH emerged as the most probable candidates to explain the course of cognitive decline in EM and EF.
Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL) is a rare hereditary cerebral small vessel disease associated with loss-of-function mutations in the High Temperature Requirement Serine Protease 1 (HTRA1). While previous mouse models have provided insight into the functions of HTRA1, they have incompletely replicated the pathogenesis of CARASIL. A novel gene-edited rat model of CARASIL (designated CRHTRA1) was generated containing the loss-of-function Htra1 mutation p.R302Q. Quantitative cognitive, physiological, pathological and transcriptomic analyses were conducted to assess the CARASIL phenotype. At 12 months, histopathological analyses revealed marked thickening of the cerebral arteriolar walls with concomitant lumen stenosis. Changes in elastic composition, vascular smooth muscle cells and extracellular matrix proteins were identified in cerebral arteries. Downstream pathological remodeling of vasculature is implicated in increased capillary tortuosity and changes in capillary coverage in specific brain regions. Focal hyperintensity regions associated with enlarged perivascular spaces were identified locally by in vivo proton density weighted MRI. Region-specific reductions of fractional anisotropy were identified using diffusion tensor imaging and correlated with a reduction in neuronal densities. Behavioral testing in CRHTRA1 rats revealed significant cognitive deficit and gait disturbances. Micro-computed tomography of spinal vertebrae revealed pronounced increases in osteophyte formation. Global cerebral RNA sequencing revealed changes in signaling pathways associated with the loss-of-function HTRA1 CARASIL mutation, including those associated with transforming growth factor-β signaling and extracellular matrix remodeling. The CRHTRA1 rat recapitulates many pathological changes that are consistent with both clinical CARASIL pathology and studies of HTRA1 function in vitro.
MRI markers, including visible perivascular spaces (PVS), diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, and peak width of skeletonized mean diffusivity (PSMD) may capture the earliest pathogenesis of cerebral small vessel disease (SVD). This study aimed to elucidate the association between these markers and cognitive decline in sporadic and hereditary SVD. We included individuals from two cohorts: (1) participants with sporadic SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance imaging Cohort (RUNDMC) and (2) participants with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) followed at the French National Referral Center. Individuals in both cohorts underwent neuroimaging and cognitive assessment over 14 years. We quantified baseline PVS burden, DTI-ALPS index and PSMD. We used linear mixed models to test their associations with longitudinal cognitive function, and Fine-and-Gray models to assess their association with incident all-cause dementia. Cohort 1 included 446 individuals (mean age (SD) 65.2 years (8.9); 203 women), Cohort 2 included 164 individuals (mean age (SD) 49.9 years (12.6); 88 women). Baseline DTI-ALPS index was independently associated with better longitudinal processing speed (Cohort 1:β=0.11, 95 %CI 0.03-0.19) and cognitive index (Cohort 2:β=0.20, 95 %CI 0.06-0.33). Neither PVS burden, DTI-ALPS index nor PSMD were significantly associated with increased risk of all-cause dementia. These findings suggest that DTI-ALPS index may serve as a marker for cognitive decline. However, these markers have limited association with all-cause dementia risk. Future studies are needed to validate DTI-ALPS index and its link to cognitive decline.
Post-stroke cognitive impairment (PSCI) affects up to one-third of stroke survivors and is a major contributor to long-term disability and reduced quality of life. Its heterogeneous phenotype reflects the interplay of acute cerebrovascular injury with chronic vascular pathology, inflammation, blood-brain barrier dysfunction, and, in many patients, coexisting neurodegeneration. Clinical manifestations vary according to lesion location and most commonly involve executive and attentional deficits, with variable impairment of memory, language, visuospatial function, and neuropsychiatric domains. Cognitive trajectories range from partial early recovery to persistent or progressive decline. Diagnosis remains challenging because covert cerebrovascular disease and overlapping neurodegenerative processes may mimic or amplify deficits. A stepwise diagnostic strategy combining focused cognitive screening, neuropsychological assessment when indicated, and neuroimaging is therefore recommended. In many acute stroke settings, CT continues to serve as the routine first-line modality, whereas MRI allows more detailed characterization where available. Emerging adjuncts include fluid biomarkers of neuroaxonal injury, inflammation, and vascular brain injury, as well as digital and telephone-based tools that may support longitudinal monitoring in selected populations. Treatment options remain limited. Non-pharmacological interventions, including cognitive rehabilitation, physical activity, and multimodal neurorehabilitation, are central to current management, although PSCI-specific high-quality evidence is scarce. Prevention is essential and should focus on vascular risk-factor control, lifestyle modification, cognitive reserve, and social engagement. This narrative review synthesizes current evidence on the mechanisms, presentation, diagnosis, and management of PSCI and highlights priorities for harmonized care pathways and the routine integration of cognitive health into stroke care.
Atherosclerosis is a leading contributor to cardiovascular disease and mortality worldwide, influenced by both genetic and environmental factors. Educational attainment, as a key socioeconomic indicator, has been consistently associated with cardiovascular risk in observational studies. However, the causal nature of this relationship remains uncertain. This study aimed to investigate the potential causal association between educational attainment and the risk of atherosclerosis using Mendelian randomization (MR) methods. We performed a two-sample MR analysis using genome-wide association study (GWAS) summary statistics. Educational attainment, measured as college completion and years of schooling, was used as the exposure, and atherosclerosis, coronary artery disease, and cerebral atherosclerosis were the outcomes. Causal estimates were obtained using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. Sensitivity analyses, including pleiotropy and heterogeneity tests, were conducted to validate the robustness of the results. Using the inverse variance weighted (IVW) method, genetically predicted higher educational attainment (college completion) was associated with a lower risk of atherosclerosis (OR = 0.43, 95 % CI: 0.32-0.57, P = 1.79E-08) and coronary artery disease (OR = 0.57, 95 % CI: 0.46-0.71, P = 6.62E-07). Additionally, an inverse association was observed between genetically predicted years of education and coronary artery disease risk (OR = 0.95, 95 % CI: 0.93-0.97, P = 2.85E-06). No significant association was found with cerebral atherosclerosis (P > 0.05). Sensitivity analyses indicated no evidence of horizontal pleiotropy or substantial bias. Although the associations did not reach statistical significance in MR-Egger or weighted mode analyses, the odds ratios remained below 1 across these methods, suggesting consistent protective trends and supporting the robustness of the findings. Our findings provide genetic evidence supporting a potential causal association between educational attainment and the risk of atherosclerosis, particularly coronary artery disease. These associations likely reflect indirect effects mediated by socioeconomic and behavioral pathways. Future research should investigate the mechanisms underlying these associations and explore how educational inequalities contribute to cardiovascular health disparities.
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Aerobic exercise may improve cerebral perfusion and may thereby attenuate, or delay, cognitive decline. Excersion-VCI aimed to evaluate the effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment (VCI). This Randomized Controlled Trial included non-demented adults ≥50 years diagnosed with VCI. Patients were randomly assigned either home-based aerobic interval training (exercise group) or information sessions (control group). Primary outcome was change in Arterial Spin Labelling MRI grey matter cerebral perfusion from baseline to 14-week follow-up. Per-protocol analysis was performed in patients who completed the follow-up. Secondary outcomes were VO2max and cognitive function. Exploratory outcomes were depression and apathy, White Matter Hyperintensities, cerebral volumes, and blood biomarkers. Fifty-eight VCI patients (mean age 67.0 ± 6.7 years) were allocated to the exercise (n = 28) or control group (n = 30). Intention-to-treat analyses showed that change in grey matter cerebral perfusion in the exercise group did not differ from the control group (p = 0.38), nor were there group differences in change in VO2max (p = 0.17). The exercise group showed an increase in triglycerides compared to the control group (p = 0.04). No group differences were found for other outcomes. Per protocol analyses showed improvement in VO2max in the exercise group compared to the control group (p = 0.04). An aerobic exercise program in VCI patients improved cardiorespiratory fitness in those who adhered to the protocol, but did not show significant effects on grey matter cerebral perfusion or other outcomes. The intervention duration of 14-weeks may have been too short to measure changes in perfusion or improvements in cognitive function.
Patients with symptomatic high degree carotid artery stenosis often exhibit a reduced perfusion pressure in the cerebral vasculature in absence of sufficient collaterals. The aim of this research was to evaluate changes in mean blood flow velocity and pulsatility within the cerebral perforating arteries following carotid endarterectomy (CEA). Fifteen patients with symptomatic high degree (>50 %) carotid artery stenosis were included in the monocentre prospective observational Carotis7T study. All patients underwent 7T magnetic resonance imaging (MRI) one day prior to CEA and three months postoperative. Mean blood flow velocity (Vmean) and pulsatility index (PI) were measured in the first segment of the middle cerebral artery (M1 of MCA), and in the perforating arteries of the basal ganglia (BG) and semi-oval centre (CSO), using a 2D phase-contrast 7T MRI sequence. Outcomes on the ipsilateral side were compared between the preoperative and postoperative situation. A postoperative increase (+14.2 %) in Vmean and (+10.7 %) in PI was seen at the level of the MCA. A slight decrease in Vmean and a slight increase in PI were observed at both the level of the BG (respectively -5.6 % and +12.8 %) and CSO (respectively -13.2 % and +11.0 %) between the preoperative and postoperative situation following CEA. However, these changes were not statistically significant. In this small single centre patient sample, our findings suggest that revascularization by removal of the stenosis and atherosclerotic plaque does not result in a measurable impact on the brain's perfusion at BG and CSO level at three months post intervention.
In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients. We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter. Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (p = 0.04) and in the basal ganglia in sporadic cSVD (p = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter. These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury.
The study intended to explore the therapeutic effect of liquiritin on PSD rats and its role in the pathogenesis of PSD. The stroke model was established via middle cerebral artery occlusion, and the PSD model was created using chronic unpredictable mild stress combined with isolated feeding. The expressions of BDNF, Bax, and Bcl-2 proteins in the hippocampus of rats were detected using Western blot and immunofluorescence staining after 6 weeks of modeling. The weight, sucrose consumption and activity of the PSD rats decreased (P < 0.05) compared with the normal control and stroke groups. On the contrary, the weights of the liquiritin and escitalopram groups increased and their sucrose consumption and activity increased in the open-field test (P < 0.05) compared with the PSD and normal saline (NS) groups.The result of immunofluorescence staining and western-blot showed that BDNF and Bcl-2 increased in the liquiritin group and Bax increased significantly in the stroke and PSD groups (P < 0.05). Liquiritin is capable of inhibiting neuronal apoptosis in the hippocampus of PSD rats to improve depression symptoms. This improvement may be achieved by reducing the expression of Bax and increasing the expressions of Bcl-2 and BDNF in the hippocampus of PSD rats.
Cerebral small vessel disease (CSVD) is a chronic, progressive disorder that affects small blood vessels in the brain's white matter. This white matter damage appears on brain imaging as white matter hyperintensities (WMH). Although CSVD is often asymptomatic, it causes one fifth of strokes and nearly half of all vascular dementia cases, highlighting its clinical importance. Statins, widely used to lower lipid levels, are effective for reducing cardiovascular mortality in high-risk groups and are recommended for patients with myocardial infarction and ischemic stroke. This systematic review and meta-analysis of randomized controlled trials aimed to evaluate the impact of statin therapy on CSVD. A literature search was performed in PubMed, Embase, the Cochrane Library and Epistemonikos resulting in the full-text review of 86 articles, of which two were used for the meta-analysis. A non-significant trend towards lower WMH volume in milliliters was observed in the statin group compared to controls, mean difference (MD) = -4.44 (95 % CI -10.19-1.31). There is limited evidence available for the use of stain-treatment for CSVD, and further research is needed as well as studies on the clinical and person-centered benefits of statins on cognition and functional level in persons with CSVD.
Cerebral microbleeds (CMBs), which present as foci of hypointensities on T2*-weighted Magnetic Resonance Imaging (MRI) are associated with weakened vessel walls. CMBs are also a frequent finding in traumatic brain injury (TBI) in association with poor outcome. We investigated whether a combination of susceptibility weighted imaging (SWI) and dynamic contrast enhanced (DCE) MRI could accurately identify characteristics of CMBs that are most relevant to TBI. Thirty TBI patients were recruited from a neurosurgical unit. We acquired structural three-dimensional T1-weighted, T2-weighted dark fluid, SWI, and DCE-MRI images on a 3T MRI. DCE-MRI data was fitted for a linear graphic (Patlak-Gjedde) model to calculate voxel-wise volume transfer constant (Ktrans) maps. Ktrans ranges of normal-appearing brain (NAB) areas were quantified and two sub-classes of CMBs-leaky and non-leaky CMBs-were identified. Characteristics and spatial distribution of the quantified imaging metrics and the immunological blood panel results were then compared across mild versus moderate-severe TBI groups, as classified by Glasgow Coma Scale. More severe TBI was associated with CMBs exhibiting leaky BBB as quantified by DCE-MRI. Higher blood levels of interferon gamma (IFN-γ) were associated with lower number of CMBs in TBI patients at more than 8 days post-TBI. combined DCE-MRI and SWI confirmed that CMBs with leaky BBBs are more prevalent in moderate-severe TBIs compared. Higher levels of IFN-γ appeared to have been associated with fewer CMBs in the sub-acute stage of TBI.