The focus of this study is to investigate the role of diffusion tensor imaging along the perivascular space (DTI-ALPS) index in brain aging. To address this, we first examined the association of DTI-ALPS with aging hallmarks among 40,488 UK Biobank (UKB) participants. Next, we developed normative brain age models incorporating the DTI-ALPS index from 12,401 healthy UKB adults and validated in UKB-ADNI and UKB-TALENT datasets. Finally, we explored the relationship between brain age gap (BAG) with peripheral organ function, chronic diseases, proteomics, and genetics, while identifying modifiable factors in a longitudinal cohort. The findings revealed that DTI-ALPS index correlated with chronological age, telomere length, brain structure, and cognition. A brain age model integrating the DTI-ALPS index achieved good accuracy in the UKB (r = 0.756) and replicated well in two independent datasets (UKB-ADNI: r = 0.766; UKB-TALENT: r = 0.724), with choroid plexus volume emerging as an additional contributor. Musculoskeletal health was a key driver for brain aging in females, while pulmonary metrics prevailed in males. Neurodegenerative and metabolic disorders increased BAGs, imparting increased mortality risk. Protein-wide and genome-wide analysis identified 154 BAG-related proteins and 11 loci. Modifiable factors, particularly systolic blood pressure below 120 mmHg, were strongly associated with reduced BAGs. Overall, the DTI-ALPS index is a promising brain aging biomarker, offering insights into links between brain and peripheral health, and highlighting sex-stratified therapeutic strategies. Aggressive blood pressure control may mitigate brain aging and promote long-term brain health.

Sleep behaviors and physical activity (PA) are widely used to predict the risk of neurodegenerative disease. However, how sleep and PA interact to influence brain and cognitive health remains unknown. This study investigated independent, joint, and interacting associations of sleep behaviors and PA with brain structures and cognitive phenotypes using linear regression and generalized linear models among over 40,000 middle-aged and older participants in UK Biobank. We first found that unhealthy sleep patterns, abnormal sleep duration and high levels of PA were each associated with worse cognitive function and brain structure damage. Joint association analyses revealed that the group with long sleep duration and low levels of PA had the greatest prevalence of white matter hyperintensities (WMH; β = 0.131, PFDR = 0.013), a key metric of brain structural changes. Interestingly, interaction analysis suggested that a high level of PA significantly mitigates brain damage in relation to long sleep duration (i.e., grey matter loss, βmoderate-long = -0.088, βhigh-long = -0.013, Pinteraction = 0.024). In terms of cognitive phenotypes, a combination of long sleep and low levels of PA was similarly associated with worse cognitive performance (i.e., symbol digit scores, β = -0.043, PFDR = 0.018). Additionally, when stratified by PA levels, long sleep duration exhibited a negative impact on cognition compared to normal sleep duration among those with low PA, but this effect was smaller or insignificant for those engaging in moderate or high PA (i.e., symbol digit scores, βlow-long = -0.047, PFDR = 0.029; βmoderate-long = -0.022, PFDR = 0.025; βhigh-long = -0.016, PFDR = 0.239). Overall, maintaining a high PA level during late middle age could potentially mitigate the detrimental effects on brain structure associated with excessive sleep. Healthy sleep habits alongside an adequate PA level are essential for maintaining brain health during aging.

Background The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact of sleep duration trajectory. This study aims to model the sleep duration trajectory as predictors for the subsequent development of cardio-metabolic disease. Methods This study recruited a notably large population (n = 9883) of subjects aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS), who participated in sequential surveys conducted in 2011, 2013, 2015, and 2018. Sleep duration trajectories were plotted using data of night sleep duration recorded at intervals from 2011 to 2015 by latent class trajectory model. The onset of cardio-metabolic diseases from 2015 to 2018 were confirmed and then the risk of different sleep duration trajectories on incident cardio-metabolic disease was examined using cox proportional hazards regression model. Results We identified four sleep duration trajectories. Compared to the normal-stable trajectory, the short-stable trajectory was significantly associated with higher risk of incident stroke (hazard ratio [HR], 1.32; 95 % confidence interval [CI], 1.02 to 1.70), dyslipidemia (HR, 1.22; 95%CI, 1.01 to 1.49), and diabetes (HR, 1.42; 95%CI, 1.13 to 1.78) within three years of follow-up, and the short-increasing trajectory predicted a higher risk of incident stroke (HR, 2.38; 95%CI, 1.25 to 4.55). Conclusions Short sleep trajectory could increase the risk of incident stroke, dyslipidemia, and diabetes, and an increasing sleep trajectory was associated with increased risk of incident stroke among middle-aged and older Chinese adults.

Background:White matter microstructure is valued for being an indicator of neural network integrity, which plays an indispensable role in the execution of advanced brain functions. Although the number of publications has increased in the past 10 years, no comprehensive analysis has yet been conducted of this field. Therefore, this study aimed to identify the research hotspots and trends in research on white matter microstructure using a bibliometric analysis of the related literature published from 2013 to 2022.Methods:VOSviewer and CiteSpace were used to objectively analyze the research articles concerning white matter microstructure, which were retrieved from the Web of Science Core Collection (WoSCC).Results:A total of 5,806 publications were obtained, with the number of published articles increasing annually over the past decade. The United States, China, the United Kingdom, and Canada maintained the top positions worldwide and had strong cooperative relationships. The top institution and journal were Harvard Medical School and Neuroimage, respectively. Alexander Leemans, Marek Kubicki, and Martha E Shenton were the most productive authors. Thematic keywords mainly included "diffusion tensor imaging" (DTI), "white matter integrity", and "connectivity". The keyword analysis revealed that DTI has a critical role in detecting white matter microstructure integrity and that fractional anisotropy is the main parameter in the assessment process. Keyword burst detection identified four research hotspots: movement, distortion correction, voxelwise analysis, and fixel-based analysis.Conclusions:This bibliometric analysis provided a systematic understanding of the research on white matter microstructure and identified the current frontiers. This may help clinicians and researchers comprehensively identify hotspots and trends in this field.

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating diseases of the central nervous system, have drawn the attention of many researchers due to the relapsing courses and cumulative disability. A first bibliometric analysis of NMOSD was conducted to identify the research hotspots and emerging trends. Articles relevant to NMOSD published in the core collection of Web of Science were retrieved and analyzed through visualized analysis using CiteSpace and VOSviewer, focusing on annual publication trends, countries, institutions, authors, journals, and keywords. The analysis showed that over the past 30 years, publications related to NMOSD had shown steady growth with slight fluctuations. The United States played an important part in this field, with the highest outputs and the greatest number of citations. Research hotspots of NMOSD had gradually shifted from the definition, biomarkers, and diagnostic criteria to diagnosis and treatment, particularly immunotherapy. This bibliometric analysis provides researchers with a theoretical basis for studying NMOSD and offers guidance for future research directions.

Spinal cord injury (SCI) leads to permanent neural dysfunction without effective therapies. We previously showed that human plurip-otent stem cell (hPSC)-derived spinal GABA neurons can alleviate spasticity and promote locomotion in rats after SCI, but whether this strategy can be translated into the clinic remains elusive. Here, a nonhuman primate (NHP) model of SCI was established in rhesus macaques (Macaca mulatta) in which the T10 spinal cord was hemisected, resulting in neural conduction failure and neural dysfunction, including locomotion deficits, pain, and spasms. Grafted human spinal GABA neurons survived for up to 7.5 months in the injured monkey spinal cord and retained their intrinsic properties, becoming mature and growing axons and forming synapses. Importantly, they are functionally alive, as evidenced by designer receptors exclusively activated by designer drug (DREADD) activation. These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.

Stroke imposes a substantial burden worldwide. With the rapid economic and lifestyle transition in China, trends of the prevalence of stroke across different geographic regions in China remain largely unknown. Capitalizing on the data in the National Health Services Surveys (NHSS), we assessed the prevalence and risk factors of stroke in China from 2003 to 2018. In this study, data from 2003, 2008, 2013, and 2018 NHSS were collected. Stroke cases were based on participants’ self-report of a previous diagnosis by clinicians. We estimated the trends of stroke prevalence for the overall population and subgroups by age, sex, and socioeconomic factors, then compared across different geographic regions. We applied multivariable logistic regression to assess associations between stroke and risk factors. The number of participants aged 15 years or older were 154,077, 146,231, 230,067, and 212,318 in 2003, 2008, 2013, and 2018, respectively, among whom, 1435, 1996, 3781, and 6069 were stroke patients. The age and sex standardized prevalence per 100,000 individuals was 879 in 2003, 1100 in 2008, 1098 in 2013, and 1613 in 2018. Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018, while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018. Across geographic regions, the central region consistently had the highest prevalence, but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018 (Ptrend<0.001), surpassing the eastern region in 2013. Advanced age, male sex, rural area, central region, hypertension, diabetes, depression, low education and income level, retirement or unemployment, excessive physical activity, and unimproved sanitation facilities were significantly associated with stroke. In conclusion, the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions. It is important to develop targeted prevention programs in underdeveloped regions. Besides traditional risk factors, more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

ObjectiveTo evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance.MethodsWe recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4.ResultsIn total, 158 participants were included in this study with a mean age of 60.5 (56.0–66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively.ConclusionsSerum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.

Background and purpose The relationship between sleep duration and stroke are inconclusive in China, especially in those individuals with metabolic syndrome. We aimed to investigate the association between sleep duration and incident stroke in participants with metabolic syndrome or its specific components in China. Materials and methods Data were taken from the 2011 and 2015 waves of China Health and Retirement Longitudinal Study (CHARLS). Habitual sleep duration (≤6, 6∼8 [reference], >8 h), daytime napping (0, 1∼60 [reference], and >60 min) were determined by self-reported questionnaires. Metabolic syndrome was defined by blood assessment and biomarkers combined with self-reported doctors’ diagnosis. Incident stroke was determined by reported stroke from 2011 to 2015 wave. Cross-sectional and longitudinal associations between sleep and (incident) stroke at baseline and 4-year follow-up period were tested among the population with metabolic syndrome and its components. Results A U-shaped relationship was observed between sleep duration and stroke in cross-sectional analysis. Sleep ≤ 6 h/night had a greater risk of incident stroke (hazard ratio [HR] 1.65; 95% confidence interval [CI] 1.04–2.61) compared with sleep 6∼8 h/night. And the HR of stroke was 1.62 (95%CI, 1.03–2.53) for sleep < 7 h/day compared to 7∼9 h/day. These associations were more evident in the female and individuals aged 45–65 years. Furthermore, the effect of short sleep duration on incident stroke was different in each component of metabolic syndrome, which was more pronounced in participants with elevated blood pressure. And a significant joint effect of sleeping ≤ 6 h/night and no napping on risk of stroke was observed (HR 1.82, 95%CI 1.06–3.12). Conclusion Short sleep duration was an independent risk factor for incident stroke, especially among females, individuals aged 45–65 years, or those with some components of metabolic syndrome, such as hypertension. Napping could buffer the risk of short sleep duration on incident stroke.

ObjectiveLow heart rate variability (HRV), an indicator of autonomic nervous system dysfunction, has been associated with increased all-cause and cardiovascular mortality and incident stroke. However, the relationship between HRV and cerebral small vessel disease (CSVD) showed contradictory results. We aimed to examine the relationship of HRV and total burden of CSVD and each of the magnetic resonance imaging (MRI) markers of CSVD.MethodsWe recruited 435 patients who attended our hospital for physical examination between June 2020 and August 2021. All underwent 24-h Holter monitoring and MRI scan. The standard deviation of normal-to-normal intervals (SDNN) was selected as the method for HRV assessment. The presence of severe white matter hyperintensity, lacunes, and >10 enlarged basal ganglia perivascular spaces, and cerebral microbleeds were added for estimating the CSVD score (0–4). Multivariate logistic analyses was performed to assess whether HRV was independently associated with the burden of CSVD and each of the MRI markers of CSVD, with and without stratification by prevalent diabetes.ResultsThis study included 435 subjects with a mean age of 64.0 (57.0–70.0) years; 49.4% of the patients were male, and 122 (28.0%) had a history of diabetes. In multivariate analyses, lower SDNN was independently associated with total burden of CSVD and the presence of enlarged perivascular spaces in all subjects. According to diabetes stratification, lower SDNN was independently associated with total burden of CSVD and each MRI markers of CSVD separately only in the diabetic group.ConclusionsLower HRV was associated with total burden of CSVD and each MRI markers of CSVD separately among diabetic patients, but not among non-diabetic patients.

Vascular cognitive impairment is the second most common cause of dementia which can be induced by chronic cerebral hypoperfusion. Regulatory T cells (Tregs) have been proven to provide beneficial effects in several central nervous system (CNS) diseases, but the roles of Tregs in chronic cerebral hypoperfusion-induced white matter damage have not been explored. In this study, Foxp3-diphtheria toxin receptor (DTR) mice treated with diphtheria toxin (DT) and wild type C57BL/6 mice treated with anti-CD25 antibody were subjected to bilateral carotid artery stenosis (BCAS). Flow cytometry analysis showed Tregs were widely distributed in spleen whereas barely distributed in brain under normal conditions. The distribution of lymphocytes and Tregs did not change significantly in spleen and brain after BCAS. Depletion of Tregs decreased the numbers of mature oligodendrocytes and anti-inflammatory microglia at 14 days and 28 days following BCAS. And pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interferon-γ (IFN-γ) showed higher expression after Tregs depletion. In contrast, Tregs depletion did not change the overall severity of white matter injury as shown by the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), luxol fast blue (LFB) staining and electron microscopy assay. Moreover, Tregs depletion had marginal effect on cognition defects after BCAS revealed by Morris water maze and novel object recognition examination at 28 days after BCAS. In summary, our results suggest an anti-inflammatory role of Tregs with marginal effects on white matter damage in mice after BCAS-induced chronic cerebral hypoperfusion.

Introduction. Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack of a large sample size of researches. This meta-analysis was performed to explore the potential association between the APOE gene and IS. Methods. To identify relevant case control studies in English publications by October 2020, we searched PubMed, Embase, Web of Science, and the Cochrane Library. Pooled odds ratios (ORs) with fixed- or random-effect models and corresponding 95% confidence intervals (CIs) were calculated to analyze potential associations. Results. A total of 55 researches from 32 countries containing 12207 IS cases and 27742 controls were included. The association between APOE gene ε4 mutation and IS was confirmed (ε4 vs. ε3 allele: pooled OR=1.374, 95% CI, 1.214-1.556; ε2/ε4 vs. ε3/ε3: pooled OR=1.233, 95% CI, 1.056-1.440; ε3/ε4 vs. ε3/ε3: pooled OR=1.340, 95% CI, 1.165-1.542; ε4/ε4 vs. ε3/ε3: pooled OR=1.833, 95% CI, 1.542-2.179; and APOE ε4 carriers vs. non-ε4 carriers: pooled OR=1.377; 95% CI, 1.203-1.576). Interestingly, APOE ε4 mutation showed a dose-response correlation with IS risk (ε4/ε4 vs. ε2/ε4: pooled OR=1.625; 95% CI, 1.281-2.060; ε4/ε4 vs. ε3/ε4: pooled OR=1.301; 95% CI, 1.077-1.571). Similar conclusions were drawn in the small artery disease (SAD) subtype, but not in large artery atherosclerosis (LAA) or in cardioaortic embolism (CE), by subgroup analysis. Conclusions. These observations reveal that specific APOE ε4 mutation was significantly associated with the risk of IS in a dose-dependent manner, while APOE ε4 mutation was related to SAD subtype onset without a cumulative effect.

BACKGROUND AND PURPOSE:Whilst retinal microvasculature represents cerebral small vessels, the retinal nerve fiber layer is the extended white matter of the brain. The aim was to investigate the correlation between changes in retina and white matter hyperintensities (WMHs).METHODS:Sixty-four candidates with WMHs received an optical coherence tomography angiography examination. WMHs were divided into mild or moderate/severe groups according to the Fazekas score. After imaging the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the microvascular density parameters (vascular perfusion density [VPD], vascular length density [VLD] and fovea avascular zone area) and morphological parameters (vessel diameter index [VDI], fractal dimension [FD] and vessel tortuosity) were identified. A software algorithm measured the thickness of the peripapillary retina nerve fiber layer (PRNFL).RESULTS:Thirty-two were classified as having mild WMHs and 32 were moderate/severe. The median (interquartile range) ages of the two groups were 58 (54-64) and 61 (57-67) years, respectively. A decrease of FD, VPD and VLD in either SCP or DCP appeared with an increased risk of moderate/severe WMHs. Although changes of capillary plexus were not associated with paraventricular WMHs, decreased FD, VPD, VLD and fovea avascular zone area in either SCP or DCP were associated with an increased risk of moderate/severe deep WMHs (DWMHs). Participants with moderate/severe WMHs demonstrated reduced PRNFL thickness, particularly in the DWMHs, compared with mild WMHs.CONCLUSIONS:Abnormalities of retinal microvascular density, morphological parameters and PRNFL thickness are correlated with the incidence of moderate/severe WMHs, particularly the DWMHs, suggesting that arteriosclerosis and hypoperfusion are the causes of DWMHs.

Background ALS patients have changed peripheral immunity. It is unknown whether peripheral immunity is related to cognitive dysfunction in ALS patients. Objective To explore the relationship between the peripheral blood lymphocyte subsets and the cognitive status in ALS patients. Methods Among 81 ALS patients, we compared the demographic, clinical, and peripheral levels of total T lymphocyte, CD4+ T lymphocyte, CD8+ T lymphocyte, B lymphocyte, and NK cell between those with cognitive impairment (ALS-ci) and those without (ALS-nci). The cognitive status was evaluated via the Chinese version of the Edinburgh cognitive and behavioral screen (ECAS). Significant predictors of cognitive impairment in univariate logistic regression analysis were further examined using multivariate logistic regression analysis. Results 39.5% of all ALS patients had cognitive impairment. The ALS-ci group had shorter education time, older age at both symptom onset and testing, longer disease duration, and lower levels of peripheral total, CD4+, and CD8+ T lymphocyte and B lymphocyte than the ALS-nci group. Frequency of behavioral impairment did not differ between the two groups. While parameters with significant differences identified by group comparison were also significant predictors of cognitive impairment in univariate logistic regression analysis except the level of B lymphocyte, only older age at testing, education time less than 9 years, and lower level of CD4+ T lymphocyte remained significant in multivariate logistic regression analysis. The predictive model combining these three parameters had an area under the receiver operating characteristic curve value of 0.842 with a sensitivity of 90.6% and a specificity of 67.3%. Conclusion In Chinese ALS patients, blood CD4+ T lymphocyte might help evaluate cognitive impairment along with age and education level.

Abstract Objective To explore dynamic changes of peripheral blood lymphocyte subsets in patients with acute ischemic stroke (AIS) and the relationship with stroke severity and long‐term outcomes. Methods A total of 96 consecutive patients with AIS and 28 age‐ and gender‐matched healthy controls were recruited. Peripheral blood samples were collected, and the percentages of lymphocyte subsets were analyzed by flow cytometry. The dynamic changes in lymphocyte subsets and their correlation with clinical parameters, such as National Institutes of Health Stroke Scale (NIHSS) scores at onset and modified Rankin scale (mRS) scores 3 months later, were evaluated. Results In our study, we observed a decrease in the percentages of T‐lymphocytes (T cells), helper/inducible T‐lymphocytes (Th cells) and suppressor/cytotoxic T‐lymphocytes (Ts cells) in AIS patients as compared to controls. The frequencies of T cells and Ts cells on day 8–14 after stroke in NIHSS ≤4 group were significantly higher than those in NIHSS >4 group. The percentages of T cells and Th cells on day 1–3 after stroke in the mRS ≤2 group were higher than those in the mRS >2 group. Conclusion The frequencies of T cells, Th cells, and Ts cells in AIS are declined dramatically at least 14 days after stroke. Lower frequencies of T cells and Ts cells on day 8–14 after stroke represent more severe disease conditions, and the percentages of T cells and Th cells within 72 hr after stroke are negatively correlated with 3‐month outcomes, which might have a potential for predicting long‐term prognosis of stroke.

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a relatively rare anti-neuronal surface antigen autoimmune encephalitis (LE). We described a case of a 47-year-old Chinese man having anti-AMPA receptor limbic encephalitis initially presented with cognitive decline, undetectable antibodies, and normal imaging findings in magnetic resonance image (MRI) and then developed into typical autoimmune limbic encephalitis a few months later with a course of multiple relapses. In addition, we found progressive brain atrophy in our case, which was a rare presentation of LE. This report also summarized the characteristics of nine reported cases of anti-AMPA receptor limbic encephalitis with relapse up to date. This case highlighted that autoimmune limbic encephalitis is an important differential diagnosis for patients with typical symptoms even when the MRI and antibodies are normal, and more attention should be paid to the relapse of anti-AMPA receptor encephalitis.

INTRODUCTION:Depression, the most prevalent mood disorder, has high comorbidity with cerebrovascular disease and cognitive decline. However, there is little understanding of the cellular mechanisms involved in depression and its comorbid cerebrovascular damage and cognition impairment. Here, we tested the prediction that the chronic unpredictable mild stress (CUMS) mouse model would manifest in disturbed glymphatic function and that dietary supplementation with polyunsaturated fatty acids (PUFA) could ameliorate these deficits while alleviating the depression-associated cognitive decline.METHODS:To test the treatment effects of PUFA or Es on behaviours, we applied the tail suspension, open field, and sucrose preference tests to assess depressive symptoms, and applied the Morris water maze test to assess cognition in groups of control, chronic unpredictable mild stress (CUMS), PUFA, and escitalopram (Es) treatment. We measured the extracellular concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in microdialysates from prefrontal cortex (PFC) by liquid chromatography mass spectrometry. Glia cells and inflammatory factors were analysed with fluorescent immunochemistry and western blot, respectively. We tested brain vasomotor function with two-photon and laser speckle imaging in vivo, and measured glymphatic system function by two-photon imaging in vivo and fluorescence tracer imaging ex vivo, using awake and anesthetized mice. Besides, we monitored cortical spreading depression by laser speckle imaging system. AQP4 depolarization is analysed by fluorescent immunochemistry and western blot.RESULTS:We confirmed that CUMS elicited depression-like and amnestic symptoms, accompanied by decreased monoamines neurotransmitter concentration in PFC and upregulated neuroinflammation markers. Moreover, CUMS mice showed reduced arterial pulsation and compliance in brain, and exhibited depolarized expression of AQP4, thus indicating glymphatic dysfunction both in awake and anesthetized states. PUFA supplementation rescued depression-like behaviours of CUMS mice, reduced neuroinflammation and cerebrovascular dysfunction, ultimately improved cognitive performance, all of which accompanied by restoring glymphatic system function. In contrast, Es treatment alleviated only the depression-like behavioural symptoms, while showing no effects on glymphatic function and depression-incident cognitive deficits.CONCLUSIONS:The CUMS depression model entails suppression of the glymphatic system. PUFA supplementation rescued most behavioural signs of depression and the associated cognitive dysfunction by restoring the underlying glymphatic system disruption and protecting cerebral vascular function.

目的:探讨经颅多普勒超声(TCD)在低流量颈动脉海绵窦瘘(CCF)中的诊断意义.方法:通过TCD对1例经DSA确诊的低流量CCF患者的血流动力学进行检测和分析,并结合文献进行回顾性分析,比较其与高流量CCF血流动力学特征的不同,总结其特殊之处.结果:本例低流量CCF患者TCD表现为眼动脉血流速度增高,频谱颅内化.搜索既往报道的关于TCD检测CCF血流动力学特征的病例.高流量CCF的TCD主要表现为:患侧颈内动脉颅外段(瘘口近端)的血流速度明显增高,搏动指数(PI)降低,呈典型的高流低阻表现;患侧大脑中动脉、大脑前动脉流速降低;颈内动脉虹吸段流速明显增高,频谱紊乱,声频嘈杂,同时可出现涡流与紊流,并可探测到相对低平的波动性的静脉血流信号;眶上静脉血流反向,有搏动性且流速增高.低流量CCF的TCD主要表现为:各血流参数无明显差异,颅底各动脉流速、PI值及频谱形态正常且基本对称.结论:TCD对于低流量CCF具有较高的筛查和诊断价值.