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White matter hyperintensities(WMH)is prevalent in the elderly population and is associated with stroke,cognition,gait instability,and neuropsychiatric symptoms.WMH burden usually increases with the growth of age.However,in recent years,there are researches found that WMH is actually dynamic variable.During the development,part of the WMH may regress,accompanied by the slowdown of brain atrophy and cognitive improvement.While,its mechanism,influencing factors and clinical significance remains unclear,and the effective treatment to reverse WMH is not clear.The article reviewed the current studies on the regression of WMH,aiming to provide reference for clinicians to actively perform intervention in the WMH related factors,promote their reversal in the early stage and improve the brain health of patients.
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Microglia are the central nervous system's resident myeloid-derived immune cells,which play a major role in the in-nate and acquired immunological responses of brain.In the ma-intenance of brain tissue function under both healthy and patho-logical conditions,microglia take a protective or damaging role,depending on cell phenotypes and functions.The traditional mi-croglia classification of pro-or anti-inflammatory phenotypes re-fers to the profile of macrophages,hence the term"brain macro-phages:has been drawn.More microglia phenotypes are being discovered as new technologies and research methods are devel-oped,and the newly discovered microglia phenotypes are often disease-,brain region-,and function-specific,providing an important foundation for studying the pathological processes un-derlying the development of specific diseases and developing ap-propriate interventions.Here,we provide a retrospective review of recent advances in the study of phenotype and function of mi-croglia,and analyze the microglial cell lineage composition and its heterogeneous function.
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Objective To explore the influencing factors of over active bladder(OAB)in patients with cerebral small vessel disease(CSVD)and its correlation with CSVD imaging markers.Meth-ods A total of 163 elderly CSVD patients admitted in our hospital from January 2021 to Decem-ber 2022 were enrolled and divided into OAB group(37 cases)and non-OAB group(126 cases)based on the results of OAB rating scale.Mini-mental State Examination(MMSE)score,Fazekas scale score,and total CSVD burden score were recorded and compared between the two groups.Results The OAB group had older age,higher urinary frequency,larger proportions of nocturia,urgency,and urge incontinence ratio,increased Fazekas score,periventricular white matter hyper-intensity(PWMH)score and deep white matter hyperintensity(DWMH)score,and elevated total CSVD burden score and lower MMSE score than the non-OAB group(P＜0.05,P＜0.01).PWMH score and DWMH score were risk factors for the occurrence of OAB(P＜0.01).The OAB score was positively correlated with Fazekas score,PWMH score,and DWMH score in the CSVD patients(r=0.533,P=0.001;r=0.462,P=0.004;r=0.398,P=0.015).The occurrence of urgency urinary incontinence was positively correlated with Fazekas score and PWMH score in the CSVD patients(r=0.352,P=0.033;r=0.346,P=0.036).Conclusion PWMH and DWMH are risk factors for OAB occurrence in CSVD patients.
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Objective:To investigate the association between regional white matter hyperintensity (WMH) volumes and cognitive impairment in Parkinson′s disease (PD) patients.Methods:The consecutive samples of PD cohort between October 2018 and August 2019 from the Department of Movement Disorders, Beijing Tiantan Hospital, Capital Medical University were retrospectively analyzed. Demographic and disease profiles, three-dimensional brain magnetic resonance imaging data were collected. Cognition was evaluated by Mini-Mental State Examination (MMSE), and mood was evaluated by Hamilton Anxiety Scale and Hamilton Depression Scale (HAMD). According to the MMSE score, patients were divided into PD with dementia group and PD without dementia group. WMH volume was automatically calculated using unidentified bright objects detector pipeline based on anatomical autonomic labeling atlas. Firstly, demographic and disease profiles, and WMH total volume were compared between groups with and without dementia. Then, partial correlation analysis [false discovery rate (FDR) corrected] and principal component (PC) regression analysis were used to assess the association between regional WMH volumes and the MMSE score.Results:Compared with PD without dementia group, PD with dementia group showed significantly higher WMH volume [5 125 (2 727, 13 718) mm 3vs 3 214 (1 959, 7 205) mm 3, Z=-2.256, P=0.024]. After adjusting for age, low density lipoprotein, cholesterol, and HAMD score, partial correlation analysis (FDR corrected) showed that WMH volumes in the right calcarine ( r=-0.204, PFDR-corrected=0.034), the right fusiform ( r=-0.180, PFDR-corrected=0.046), the right lingual ( r=-0.146, PFDR-corrected=0.047), the left middle temporal ( r=-0.168, PFDR-corrected=0.047), the left inferior parietal lobes ( r=-0.145, PFDR-corrected=0.047) and the right inferior parietal lobes ( r=-0.148, PFDR-corrected=0.047) were significantly associated with MMSE score. PC regression analysis demonstrated that MMSE score was significantly associated with PC2 ( B=-0.632, 95% CI -1.222--0.041, P=0.036), PC13 ( B=-1.384, 95% CI -2.155--0.613, P=0.001), and PC14 ( B=-0.913, 95% CI -1.599--0.227, P=0.009); PC2, PC13 and PC14 were mainly composed of temporo-parieto-occipital WMHs in the posterior brain, and the related WMH components accounted for 9.668% of WMH variance. Conclusions:The posterior WMH burden may be associated with cognitive impairment in PD patients. However, WMH burden may not be the main contributor to cognitive impairment in PD patients.
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Objective:To investigate the association of white matter hyperintensities (WMHs) with long-term stroke recurrence in patients with recent subcortical small infarcts (RSSIs).Methods:Consecutive patients admitted to the Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University between January 2019 and August 2022 and met the clinical and imaging manifestations of RSSIs were collected. The demographic characteristics, baseline clinical data, and MRI features were collected. Using stroke recurrence as the endpoint event, the recurrence time was recorded, and Cox regression model was used to analyze relevant factors affecting stroke recurrence in patients with RSSIs.Results:A total of 202 patients were enrolled, including 138 males (68.3%), aged 67.9±10.5 years. Seventy-seven patients (38.1%) were mild WMHs, 64 (31.7%) were moderate WMHs, and 61 (30.2%) were severe WMHs. There were statistically significant differences in age, history of stroke, hypertension, hyperlipidemia, total cholesterol, infarct thickness, and infarct distribution among different WMHs severity groups (all P<0.05). The median follow-up time was 40.5 months (interquartile range, 27.7-49.0 months), and a total of 55 patients (27.2%) had stroke recurrence (ischemic stroke 54, occipital hemorrhage 1). Recurrence rates of stroke in the mild, moderate, and severe WMHs groups were 18.2%, 31.3%, and 34.4%, respectively. Cox regression analysis showed that WMHs were an independent risk factor for stroke recurrence (compared to the mild group, the risk ratio of the severe group was 2.225, 95% confidence interval was 1.116-4.436; P=0.023). Conclusion:The risk of long-term stroke recurrence in patients with RSSI is associated with the severity of WMHs.
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Nowadays,with the improvement of people's living standards and the acceleration of the aging process of population,cerebral small vessel disease has seriously endangered the life health and quality of life of the elderly.Hypertension has been paid more and more attention as an important risk factor of cerebral small vessel disease.However,in the management of hypertension,people generally concentrate on the influence of mean arterial pressure,ignoring the role of variability and circadian rhythm of blood pressure nowadays.By expounding the pathogenesis of cerebral small vessel disease and the recent studies on blood pressure variability and circadian rhythm of blood pressure,this review discusses a series of scientific problems such as the effects of blood pressure variability and circadian rhythm of blood pressure on the occurrence and development of cerebral small vessel disease.
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Objective To investigate the microstructural changes of temporal lobe epilepsy(TLE)in patients with sleep disorders based on diffusion kurtosis imaging(DKI).Methods This research prospectively included 38 TLE patients(case group)and 20 healthy controls(HC)(HC group).Participants used sleep questionnaires to evaluate their sleep status.All TLE patients were divided into groups with and without sleep disorders according to the diagnostic criteria and scale scores of sleep disorders.The mean kurtosis(MK),mean diffusivity(MD),and fractional anisotropy(FA)of the relevant region of interest(ROI)were measured by DKI sequence.The differences of sleep quality scores and DKI parameters between groups were further compared via independent samples t-test and one-way analysis of variance.Results The Epworth sleepiness scale(ESS),Athens insomnia scale(AIS),and Pittsburgh sleep qual-ity index(PSQI)scores of TLE patients with sleep disorders were significantly higher than those of HC group(P＜0.05).The FA and MK values in TLE patients were significantly lower than those in HC group,while the MD value of TLE patients were substan-tially higher than that of HC group(P＜0.05).The values of MK and FA in left TLE patients with sleep disorders were significantly lower than those of without sleep disorders(P＜0.05),while there was no significant difference in MD value between the two groups(P＞0.05).MK value of right TLE patients with sleep disor-ders was significantly lower than that of without sleep disorders(P＜0.05),however,there were no significant differences in MD and FA values between the two groups(P＞0.05).Conclusion Quantitative DKI analysis revealed differences in DKI parameters in TLE patients combined with sleep disorders,inferring a specific white matter fiber damage in this group and providing imaging data to support the personalized treatment and prognostic assessment of these patients.
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Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.
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Microglia are the central nervous system's resident myeloid-derived immune cells, which play a major role in the innate and acquired immunological responses of brain. In the maintenance of brain tissue function under both healthy and pathological conditions, microglia take a protective or damaging role, depending on cell phenotypes and functions. The traditional microglia classification of pro- or anti-inflammatory phenotypes refers to the profile of macrophages, hence the term “brain macrophages:has been drawn. More microglia phenotypes are being discovered as new technologies and research methods are developed, and the newly discovered microglia phenotypes are often disease-, brain region-, and function-specific, providing an important foundation for studying the pathological processes underlying the development of specific diseases and developing appropriate interventions. Here, we provide a retrospective review of recent advances in the study of phenotype and function of microglia, and analyze the microglial cell lineage composition and its heterogeneous function.
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BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.
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Objective:To evaluate the detective effect of double inversion recovery (DIR) sequence on cerebral white matter hyperintensities (WMH) in patients with acute ischemic stroke, and compare with those of T2WI and FLAIR sequences.Methods:Seventy-three acute ischemic stroke patients with WMH within 14 d of onset, admitted to Department of Neurology, Beijing Shijitan Hospital, Capital Medical University from November 2018 to March 2021, were chosen. MRI T2WI, FLAIR and DIR sequences were used to detect WMH. According to Fazekas scale, patients with periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH) were divided into mild group (score of 0-1) and moderate to severe group (scores≥2); the differences in WMH volume detected by T2WI, FLAIR and DIR sequences, and signal intensity, cross-sectional area and contrast of isolated lesions were compared.Results:(1) Seventy-three patients were with PVWMH (36 into the mild group and 37 into the moderate to severe group); in patients from the moderate to severe group, PVWMH volume detected by FLAIR sequence was statistically larger compared with that by DIR sequence, and PVWMH volume detected by T2WI sequence was significantly smaller compared with that by FLAIR sequence ( P<0.05). Fifty-seven patients were with DWMH (44 into the mild group and 13 into the moderate to severe group); the DWMH volume detected by FLAIR and T2WI sequences was significantly larger than that by DIR sequence ( P<0.05). (2) A total of 60 isolated lesions were detected, ranged 5.0-9.1 mm in length; isolated lesions enjoying significantly larger cross-sectional area, higher signal intensity, and lower contrast detected by FLAIR and T2WI sequences compared with those by DIR sequence ( P<0.05); isolated lesions enjoying significantly higher signal intensity and contrast detected by T2WI sequence compared with those by FLAIR sequence ( P<0.05). Conclusion:DIR sequence enjoys better effect in detecting WMH than FLAIR and T2WI sequences; the mismatch area of DIR sequence with FLAIR or T2WI sequences suggests WMH penumbra.
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Introducción: El trastorno afectivo bipolar (TAB) se ha asociado con una disminución de la integridad de la sustancia blanca. Los estudios con imágenes con tensor de difusión (DTI) han permitido elucidar con una mayor calidad estos cambios. Debido a la gran heredabilidad del TAB, se han realizado estudios en familiares de pacientes con TAB acerca de la integridad de la sustancia blanca, y se ha encontrado que la conectividad estructural también puede estar afectada. Dicha alteración se ha propuesto como un potencial biomarcador de vulnerabilidad a este trastorno. Sin embargo, los estudios en niños y adolescentes son pocos. Objetivo: Revisar la literatura sobre los cambios en la integridad de la sustancia blanca determinados mediante DTI en niños y adolescentes con alto riesgo. Resultados: Se describe la conectividad estructural cerebral en la población pediátrica en estudios que utilizaron DTI. Se describen los cambios en el proceso de mielinización desde su evolución dentro del neurodesarrollo normal hasta los hallazgos en la anisotropía fraccional (AF) en pacientes con TAB y los familiares en alto riesgo. Conclusiones: Los estudios demuestran que tanto pacientes con TAB como sus familiares en riesgo presentan disminución de la AF en regiones cerebrales específicas. Los estudios en niños y adolescentes con riesgo familiar de TAB señalan una AF reducida en tractos axonales implicados en funciones emocionales y cognitivas. La disminución de la AF puede considerarse como un biomarcador de vulnerabilidad al TAB.
Introduction: Bipolar disorder (BD) has been associated with a decrease in white matter integrity. Diffusion tensor imaging (DTI) studies have enabled these changes to be elucidated with higher quality. Due to BD's high heritability, some studies have been conducted in relatives of BD patients looking at white matter integrity, and have found that structural connectivity may also be affected. This alteration has been proposed as a potential BD biomarker of vulnerability. However, there are few studies in children and adolescents. Objective: To conduct a review of the literature on changes in white matter integrity determined by DTI in high-risk children and adolescents. Results: Brain structural connectivity in the paediatric population is described in studies using DTI. Changes in the myelination process from its evolution within normal neurodevelopment to the findings in fractional anisotropy (FA) in BD patients and their high-risk relatives are also described. Conclusions: Studies show that both BD patients and their at-risk relatives present a decrease in FA in specific brain regions. Studies in children and adolescents with a high risk of BD, indicate a reduced FA in axonal tracts involved in emotional and cognitive functions. Decreased FA can be considered as a vulnerability biomarker for BD.
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@#Stenosis and occlusion caused by carotid atherosclerosis is an important cause of ischemic stroke. In recent years, with the continuous development of magnetic resonance imaging (MRI) technology and the introduction of complex network theory, brain network analysis can be used not only to explain the clinical symptoms and cognitive dysfunction in patients with carotid stenosis caused by changes in network topological properties of different brain regions, but also to explore the imaging markers of carotid stenosis, thus providing important reference data for the diagnosis of early asymptomatic carotid stenosis, the selection of individualized intervention programs, and the assessment of efficacy. Brain network analysis has been used as a powerful tool. In this paper, we review the studies of structural and functional brain networks in patients with carotid stenosis, and introduce the definitions of brain network nodes and edges and important topological properties of complex networks. We also analyze the current research on brain network in patients with carotid stenosis, and discuss the challenges and outlook of existing imaging techniques and network construction methodologies in this field.
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OBJECTIVE@#To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines.@*METHODS@#A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared.@*RESULTS@#After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05).@*CONCLUSION@#Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.
الموضوعات
Child , Humans , Cerebral Palsy/therapy , Interleukin-33 , Diffusion Tensor Imaging/methods , Scalp , Muscle Spasticity , Tumor Necrosis Factor-alpha , Acupuncture Therapy , Cytokinesالملخص
Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.
الموضوعات
Humans , Integrative Medicine , Brain/pathology , Cerebral Small Vessel Diseases/pathology , Stroke/complications , Cognitive Dysfunction/complications , Magnetic Resonance Imagingالملخص
Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.
الموضوعات
Animals , Neuroglia/metabolism , Central Nervous System/metabolism , Astrocytes/metabolism , Oligodendroglia/metabolism , Cerebral Small Vessel Diseases/metabolism , Antigens/metabolism , Mammals/metabolismالملخص
The role of white matter of brain has always been neglected by scholars.With the development of neuroimaging technology,the role of white matter has attracted increasing attention.Perioperative neurocognitive disorders have been a hot issue in the research on anesthesia,and recent studies have suggested that white matter may be involved in the effects of general anesthetics on cognitive function.This paper reviews the progress in the relationship between white matter,general anesthesia,and cognitive function from clinical practice and research,aiming to provide new ideas for the research on the mechanism.
الموضوعات
White Matter , Cognition , Brain , Neuroimaging , Anesthesia, Generalالملخص
OBJECTIVE@#Exosomal long noncoding RNAs (lncRNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lncRNAs in white matter hyperintensities (WMH).@*METHODS@#We used high-throughput sequencing to determine the differential expression (DE) profiles of lncRNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using qRT-PCR. The diagnostic potential of candidate exosomal lncRNAs was proven by binary logistic analysis and receiver operating characteristic (ROC) curves. The diagnostic value of DE exo-lncRNAs was determined by the area under the curve (AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lncRNAs in the subgroup was evaluated.@*RESULTS@#In our results, four DE exo-lncRNAs were identified, and ROC curve analysis revealed that exo-lnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.@*CONCLUSION@#Plasma exosomal lncRNAs have potential diagnostic value in WMH. Moreover, exo-lnc_011797 is considered to be a predictor of the severity and location of WMH.
الموضوعات
Humans , RNA, Long Noncoding/genetics , White Matter , Area Under Curve , Exosomes/genetics , High-Throughput Nucleotide Sequencingالملخص
Objective To investigate the changes in plasma amyloid-β (Aβ) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aβ42 and Aβ40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aβ42,Aβ40,and Aβ42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aβ42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aβ42 level showed no significant difference among the three groups (P=0.227).The plasma Aβ40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aβ42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aβ42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aβ42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aβ42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aβ levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aβ levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.
الموضوعات
Humans , Diffusion Tensor Imaging , White Matter/diagnostic imaging , Cognitive Dysfunction , Outpatients , Cognition , Amyloid beta-Peptidesالملخص
Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.