Research progress on phenotype and function of microglia / 中国药理学通报

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.

Relationship between cerebrovascular reserve capacity and white matter lesions in the elderly based on magnetic resonance imaging / 中国辐射卫生

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.

¿Es diferente la conectividad estructural en niños y adolescentes familiares de pacientes con trastorno bipolar? Una revisión narrativa según estudios con DTI

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.

Electroacupuncture stimulation attenuates corpus striatum white matter injury in rats with cerebral ischemia by inhibition of Nogo-A/NgR pathway / 针灸推拿医学（英文版）

Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.

The effects of transcranial direct current stimulation on cognition and white matter fiber integrity in stroke patients / 中华物理医学与康复杂志

Objective:To observe any effect of transcranial direct current stimulation (tDCS) on the cognition of stroke survivors and the integrity of their white matter fibers.Methods:Thirty persons with post-stroke cognitive impairment (PSCI) were randomly divided into an experimental group ( n=15) and a control group ( n=15). In addition to basic drug therapy and routine cognition training, the experimental group received 20 minutes of tDCS daily, 5 days per week for 3 weeks, while the control group received sham tDCS stimulation. Before and after the treatment, both groups′ cognitive functioning was evaluated using the mini-mental state examination (MMSE) and the Montreal cognitive assessment scale (MoCA). Their ability in the activities of daily living (ADL) was quantified using the modified Barthel index (MBI). Diffusion tensor imaging (DTI) was employed to observe any changes in the integrity of their white matter fibers. Results:The average MMSE, MOCA and MBI scores of both groups had improved significantly after the treatment, but the improvement in the experimental group was significantly greater than among the controls. The average fractional anisotroposy value of the affected inferior fronto-occipital fasciculus in both groups was positively correlated with the group′s average MMSE score and MoCA score.Conclusion:tDCS can effectively improve the cognition and functioning in the activities of daily living of stroke survivors. Its mechanism may be related to improving the integrity of the white matter fibers involved.

Etiological analysis of single small subcortical infarction with different imaging features / 中华神经科杂志

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease / 中华神经科杂志

Objective:To investigate the relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease (CSVD).Methods:One hundred and fifty-six patients with CSVD who were admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University or the Public People′s Hospital of Xinzheng from January 2020 to May 2022 were selected, and their brain artery remodeling (BAR) score was calculated. The patients with BAR score≤-1 standard deviation (SD) were defined as individuals with constrictive remodeling of intracranial arteries, and the patients with BAR score≥1 SD were defined as individuals with dilated remodeling of intracranial arteries. Imaging markers of CSVD [white matter hyperintensities (WMHs), lacune, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy] were quantified, total CSVD load was calculated and patients were divided into low load group (0-2 points, n=91) and high load group (3-4 points, n=65) according to the total CSVD load scores. The correlation between intracranial artery remodeling and various imaging markers of CSVD and total load was analyzed by using univariate analysis and binary Logistic regression analysis. A nomogram prediction model was established and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of intracranial artery remodeling on high total CSVD load. Results:Dilated intracranial arterial remodeling was an independent influence factor on severe WMHs ( OR=3.66, 95% CI 1.38-9.72, P=0.009), lacune ( OR=3.78, 95% CI 1.17-12.19, P=0.026), cerebral atrophy ( OR=3.11, 95% CI=1.10-8.81, P=0.033), and high total CSVD load ( OR=6.66, 95% CI=2.14-20.77, P=0.001). Age was an independent influencing factor for high total CSVD load ( OR=1.12, 95% CI 1.07-1.16, P<0.01). A nomogram prediction model for high total CSVD load with age and BAR score≥1 SD as dependent variables had a good effect (C-index=0.826) and calibration ( P=0.024). The best cut-off point of ROC curve was 0.50, with an area under the curve of 0.83 (95% CI 0.76-0.89, P<0.01), the sensitivity and specificity of 0.72 and 0.82. Conclusions:Patients with dilated intracranial arterial remodeling may have a heavier CSVD load. Dilated intracranial arterial remodeling may serve as a new biomarker for assessing CSVD, but the mechanism of the association needs further study.

Structural asymmetries in neonatal brain white matter: a diffusion tensor imaging study / 中华放射学杂志

Objective:To explore the asymmetry of neonatal brain white matter using fractional anisotropy (FA) parameter generated from diffusion tensor imaging (DTI).Methods:From January 2011 to June 2013, 88 neonates with normal cranial MRI performance, aged 1-14 (7.7±0.3) days and gestational age 31-42 (37.5±0.3) weeks, were retrospectively collected from the First Affiliated Hospital of Xi′an Jiaotong University. According to the gestational age at birth, the neonates were divided into preterm group (37 cases) and term group (51 cases). DTI was processed to generate FA parametric maps. Tract-based spatial statistics (TBSS) was used to analyze the asymmetry in neonatal white matter. Regions of interest were placed in bilaterally symmetrical white matter tracts. The white matter tracts included the bilateral anterior thalamic radiation, corticospinal tract-posterior limb of the inner capsule (CST-IC), corticospinal tract-corona radiata, cingulum hippocampus part (CGH), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus, superior longitudinal fasciculus temporal part (SLF-temp). The FA value was measured and asymmetry index (AI) was calculated. The independent-sample t test or Mann-Whitney U test was used to compare the AI of each tract between the preterm and term groups. Partial correlation was used to analyze the effects of neonatal gestational age and birth anthropometric measures on the asymmetry of neonate at birth. Results:The results of TBSS showed that the left lateralized areas of brain white matter in the neonatal period were mainly located in the corticospinal tract, external capsule and genu of corpus callosum. The right lateralized areas of brain white matter in the neonatal period were mainly located in the optic radiation and splenium of corpus callosum. In both the preterm and term groups, the tracts related to motor (CST-IC) and language function (ILF, SLF, SLF-temp) were left asymmetry. The CGH of the preterm and the term neonates were right asymmetry, and AI was -0.086±0.114 and -0.140±0.108 respectively, with a statistically significant difference ( t=2.27, P=0.026), while the differences of AI in the remaining tracts were not statistically significant ( P>0.05). Only gestational age was correlated with the AI of ILF ( r=0.234, P=0.033), SLF ( r=0.259, P=0.018), SLF-temp ( r=0.252, P=0.022), CST-IC ( r=0.235, P=0.033). No significant correlation was found between birthweight, head circumference, body length and AI. Conclusions:The asymmetries of brain white matter already exist in neonates aged less than two weeks. The tracts associated with motor and language function are predominantly left asymmetry.

In vivo MRI study of the oxidative stress level in the white matter of patients with relapsing-remitting multiple sclerosis / 中华放射学杂志

Objective:To explore the oxidative stress of cerebral white matter lesion (WML) and normal-appearing white matter (NAWM) with in vivo proton exchange rate (k ex) MRI on relapse-remitting multiple sclerosis (RRMS) patients. Methods:Clinical and imaging data of 37 patients (case group) with RRMS patients of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology were analyzed retrospectively from November 2018 to November 2021, including 11 males and 26 females aged 18-41 (29±7) years. Another 22 age-matched healthy volunteers (control group) were recruited for the same period, including 4 males and 18 females aged 23-44 years with a median age of 25 (24, 28.25) years. All subjects received conventional MR protocols and chemical exchange saturation transfer imaging. The manifestation of WML on the k ex map and T 1WI images were assessed while the k ex values of WML, NAWM and normal white matter (NWM) of control group were quantitatively evaluated. Student′s t test was used to compare the k ex difference of WML and NAWM in the case group, NAWM in the case group and NWM in the control group, low-signal and isosignal WML in T 1WI. Spearman rank correlation was used to analyze the correlation of the k ex values of WML with patients′ expanded disability status scale (EDSS) score. Results:A total of 272 WML were found in the 37 RRMS patients, and 25.4% (69/272) were T 1-hypointense. The k ex value of WML in the case group [(932±108) s -1] was higher than that of NAWM [(771±26) s -1], and the difference was statistically significant ( t=8.95, P<0.001); the k ex value of NAWM in the case group [(771±26) s -1 ] was higher than that of NWM [(745±26) s -1] in the control group, and the difference was statistically significant ( t=3.96, P<0.001). The k ex value [(1 039±110) s -1] of WML with low signal at T 1WI was higher than that of WML with equal signal [(895±79) s -1], with a statistically significant difference ( t=9.78, P<0.001). Correlation analysis showed that the k ex value of WML in the case group was positively correlated with the EDSS score ( r=0.54, P<0.001). Conclusions:The elevated k ex values of WML and NAWM reflect the cerebral oxidative stress of RRMS patients and are positively correlated to the severity of tissue damage, which suggests the role of oxidative stress in RRMS lesion formation and brain atrophy.

Diagnosis model of the white matter injury of premature infants based on ultrasonography radiomics / 中华超声影像学杂志

Objective:To investigate the value of the ultrasonography in the diagnosis of the white matter injury of premature infants based on gray-scale ultrasonography radiomics.Methods:A total of 256 premature infants in Huazhong University of Science and Technology Union Shenzhen Hospital and Shenzhen Hospital of Southern Medical University from August 2018 to April 2022 were analyzed retrospectively. The computer-generated random numbers were assigned to the training set and the verification set according to 6∶4 ratio. On the basis of standardized collection of craniocerebral ultrasound images, the radiomics features were extracted from imaging by Pyradiomics 3.0.1 software package, the Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) and stepwise regression were used to select the optimal features. Then the Logistic regression was used to build radiomics model. According to MRI, ROC curve was utilized to evaluate the performance of the model. The craniocerebral ultrasound images in the validation set were independently diagnosed by a senior physician and a junior physician, and then the above two physicians diagnosed again with the help of the radiomics, and the diagnostic abilities of this model were compared with those of the junior and senior physicians with and without radiomics assist. Results:A total of 5 optimal features were selected to develop radiomics model. The sensitivity, specificity, accuracy and the area under the ROC curve (AUC) in the training and validation sets were 0.861, 0.775, 0.799, 0.818; 0.929, 0.824, 0.853, 0.876, respectively. The sensitivity, specificity, accuracy and AUC in the senior sonographer, the junior sonographer, and both of them with radiomics assist for the dagnosis in the validation set were 0.929, 0.892, 0.902, 0.910; 0.714, 0.743, 0.735, 0.729; 0.929, 0.919, 0.922, 0.924; 0.857, 0.824, 0.833, 0.841, respectively. Performance of radiomics model reached the level of the senior sonographer (AUC: 0.876 vs 0.910, P=0.284), which was significantly better than the performance of the junior sonographer(AUC: 0.876 vs 0.729, P=0.001). Performance of the junior sonographer with radiomics assist was significantly better than the performance of the junior sonographer(AUC: 0.841 vs 0.729, P=0.003). Performance of the senior sonographer with radiomics assist was comparable to that of the senior sonographer(AUC: 0.924 vs 0.910, P=0.156). Conclusions:The ultrasound diagnosis method based on radiomics technology shows good diagnostic performance for the white matter injury of premature infants. It is helpful to improve the diagnostic ability of junior sonographer. It is expected to assist the sonographers in diagnosis and provide objective, consistent and accurate results for clinical practice.

Research progress in pathogenesis of white matter hyperintensity related dizziness in small cerebral vascular disease / 中国综合临床

With the development of neuroimaging technology, cerebral small vessel disease has become a hot research topic in recent years. It has been clearly related to cognitive decline, dementia and gait instability. However, recent studies have found that small cerebral vascular disease with white matter hyperintensities is the main cause of chronic dizziness in the elderly, but the pathogenesis is not completely clear, which may be related to brain neural network disconnection, visual dependence, eye movement disorder caused by abnormal brain tissue structure, oxidative stress regulation disorder, cerebral blood flow self-regulation disorder, and the interaction mechanism between vestibular system and emotional disorder.

Research advance in changes of brain white matter in cerebral small vessel disease with cognitive impairment / 中华行为医学与脑科学杂志

With the progress of population aging, cerebral small vessel disease is increasingly becoming a common and frequent disease threatening human health, which is a common reason leaing to cognitive function decline.The changes of white matter, especially white matter hyperintensities, are the most common and typical imaging marker of small cerebral vascular disease.In recent years, a number of studies has found that white matter hyperintensities are associated with cognitive decline.These studies mainly focused on the relationship between white matter hyperintensities and cognitive frailty, and the correlation between the size, location and dynamic evolution of white matter hyperintensities and cognitive impairment of small cerebral vascular disease.Functional magnetic resonance imaging studies also revealed that patients with cognitive impairment of cerebral small vessel disease had abnormal white matter changes and structural network connectivity.Structural network can be used for quantitative analysis because of its good stability.Diffusion tensor imaging and quantitative measurement of multi-dimensional structural network were used qualitatively.It was found that the structural network integrity was damaged, the network connection efficiency was reduced, and the connection was interrupted within the white matter hyperintensity.Big data and artificial intelligence research can make early prediction of white matter hyperintensity and structural networks in patients with cerebral small vessel disease with cognitive impairment.These studies provide a reliable basis for the discovery of abnormal microstructure and network changes in the early stage of white matter hyperintensities in cerebral small vessel disease with cognitive impairment.The paper reviews the research progress of white matter hyperintensity and brain structural network in patients with cognitive impairment of cerebral small vessel disease in recent years, and in order to improve the early diagnosis of the disease and promote the early prevention and treatment.

The protective effects and mechanisms of melatonin on white matter damage in neonatal rats / 中国新生儿科杂志

Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.

Red blood cell distribution width and white matter hyperintensities / 国际脑血管病杂志

Dementia is one of the age-related diseases with the fastest increase in incidence. With the increasingly severe aging problem of the population, it further exacerbates the demand and burden of the healthcare system. Red blood cell distribution width (RDW) is an easily obtainable blood routine indicator that reflects the variability of red blood cell size. As an early marker of dementia risk, researches have shown an association between white matter hyperintensities (WMHs) and RDW. This article reviews the relationship between RDW and WMHs.

Correlation between serum lipoprotein (a) and the severity of white matter hyperintensities in middle-aged and elderly people in the community / 国际脑血管病杂志

Objective:To investigate the correlation between serum lipoprotein (a) [LP(a)] and the severity of white matter hyperintensities (WMHs) in the middle-aged and elderly people in the community.Methods:Consecutive middle-aged and elderly residents residing in the community underwent physical examinations in the Affiliated Jiangning Hospital of Nanjing Medical University from June 2016 to August 2021 were retrospectively collected. Fasting venous blood was collected on the next day of admission to detect the level of Lp(a). During hospitalization, cranial MRI examination was performed and the severity of WMHs was graded using the Fazekas visual scoring method. Ordinal multivariate logistic regression analysis was used to determine independent related factors for the severity of WMHs.Results:A total of 1 752 patients were included in the analysis. There were 969 males (55.31%) and 783 females (44.69%). Their age was 66.18±10.32 years old. There were 1 167 patients (66.61%) in the mild WMHs group, 407 (23.23%) in the moderate WMHs group, and 178 (10.16%) in the severe WMHs group. Ordinal multivariable logistic regression analysis showed that after adjusting for confounding factors, a higher serum Lp(a) level was independently related to the severity of WMHs (with the first quartile as a reference, the third quartile: odds ratio 1.441, 95% confidence interval 1.050-1.976, P=0.023; the fourth quartile: odds ratio 1.717, 95% confidence interval 1.252-2.354, P=0.001). Conclusion:Serum Lp(a) is independently correlated with the severity of WMHs.

Diffusion magnetic resonance imaging of patients with cerebral small vessel disease related cognitive impairment / 国际脑血管病杂志

Cerebral small vessel disease (CSVD) is a group of pathological, imaging and clinical syndromes involving small cerebral vessels with different causes. The incidence rate of CSVD increases with age and is the most important cause of vascular cognitive impairment. Different diffusion imaging techniques can quantify white matter microstructure damage by revealing the diffusion movement of water molecules in specific brain tissues, explore the basis and biophysical mechanisms of tissue change, and have important value for the mechanism research, early diagnosis, progression risk, and therapeutic evaluation of cognitive impairment related to CSVD. This article reviews the research progress of diffusion magnetic resonance imaging in CSVD related cognitive impairment.

Correlation between white matter hyperintensities and outcome after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between different degrees of white matter hyperintensities (WMHs) and outcome after intravenous thrombolysis (IVT) in patients with acute ischemic stroke.Methods:Patients with AIS received intravenous thrombolytic therapy with standard dose of alteplase in the First Hospital of Putian City from January 2019 to June 2022 were retrospectively included. The Fazekas scale was used to score the WMHs shown on MRI, and the patients were divided into without or mild WMH group and moderate-to-severe WMH group. The clinical baseline data and the clinical outcome after 3 months of the two groups were compared. The poor outcome was defined as the modified Rankin scale score >2. Multivariate logistic regression analysis was used to determine the influence of the severity of WMHs on the outcome after intravenous thrombolysis. Results:A total of 103 patients with AIS were included. Their age was 64.85±10.89 years old, and 66 (64.1%) were men. There were 60 patients (58.3%) in the without or mild WMH group, and 43 (41.7%) in the moderate-to-severe WMH group. There were significant differences in age, body mass index, systolic blood pressure, baseline National Institutes of Health Stroke Scale (NIHSS) scores, as well as the proportion of patients with hypertension, smoking, hemorrhagic transformation and poor functional outcome at 3 months after onset in different degrees of WMH groups (all P<0.05). There were 73 patients (70.9%) in the good outcome group and 30 (29.1%) in the poor outcome group. There were significant differences in age, body mass index, baseline NIHSS score, WMH score, as well as the proportion of patients with hypertension, large atherosclerotic stroke and symptomatic intracranial hemorrhage between the two groups ( P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, moderate-to-severe WMHs were the independent risk factors for the poor outcome at 3 months after intravenous thrombolysis (odds ratio 3.810, 95% confidence interval 1.298-1.124; P=0.015). Conclusion:Moderate-to-severe WMHs are associated with the poor outcome in patients with AIS at 3 months after intravenous thrombolysis.

Mechanism of white matter lesion in patients with CADASIL / 国际脑血管病杂志

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a common hereditary cerebral small vessel disease, and white matter lesion is its classic pathological feature. MRI showed T 2 white matter hyperintensity, its pathogenesis is complex, and the effective preventive measures are still lacking. This article reviews the possible mechanism of white matter lesion in patients with CADASIL, and provides new ideas for clinical alleviation of white matter lesion and improvement of prognosis.

Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy / 中国针灸

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.

Changes in Plasma Amyloid-β Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment / 中国医学科学院学报

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.