Background:White matter lesion(WML)is common in aging brain and is associated with cognitive impairment and dementia.However,recent studies reported an association between patent foramen ovale(PFO)and WML in migraineu...Background:White matter lesion(WML)is common in aging brain and is associated with cognitive impairment and dementia.However,recent studies reported an association between patent foramen ovale(PFO)and WML in migraineurs,especially in young,middle-aged migraineurs.Our retrospective,case-control study aims to describe the clinical characteristics of WML in this population and to explore potential risk factors.Methods:226 patients with migraine and PFO were consecutively initially screened.Relevant factors were selected by the least absolute shrinkage and selection operator(LASSO)regression and multivariable logistic regression model.A Nomogram was employed to visualize the prediction model conveniently.The discrimination and calibration abilities were evaluated using the Receiver Operating Characteristic(ROC)curve,the Hosmer-Lemeshow test,and calibration curves.Results:One hundred and nineteen participants were ultimately enrolled in our study,with a median age of 36.9±12.7 years and 80.7%of females.Brain magnetic resonance imaging MRI showed 67(56.3%)patients had WML,whereas 52(43.7%)patients were categorized into the non-WML group.LASSO regression screened out potential variables and subsequent multivariate analysisfinally identified age,mean platelet volume,andfibri-nogen(FIB)as independent predictive factors of WML.The area under the ROC curve(AUC)was 0.807.Hos-mer-Lemeshow test and calibration curve verified a consistency between the predicted and actual probability.Conclusion:The predictive nomogram established and validated in our study may assist clinicians in screening WML among young middle-aged migraineurs with PFO and developing individualized preventive and treatment strategies.展开更多
Objective:To explore whether maternal stress exposure during pregnancy impairs cognitive function and white matter ultrastructure in offspring mice.Methods:The parent rats were divided into two groups:pressure exposur...Objective:To explore whether maternal stress exposure during pregnancy impairs cognitive function and white matter ultrastructure in offspring mice.Methods:The parent rats were divided into two groups:pressure exposure group(group PE)and control group(group C),and the positive date of vaginal smear of female SD rats was day 0 of gestation.Female mice in group PE were exposed to binding pressure(3 times/day)on day 14-20 of gestation for 45 min-1 h/time.Behavioral tests(Morris water maze and Y maze)were performed on 1-month-old offspring mice followed by cardiac perfusion of fixed brain specimens and placement in mixed fixative solution.The total volume of white matter,total length and volume of myelinated nerve fibers and total length and volume of myelin sheath were calculated using modern stereoscopic methods,and the inner and outer diameter and inner and outer circumference of the myelin sheath were analyzed.Results:1)Behavioral tests:compared with the group C,the average latency of the 3th and 4th day in the group PE were significantly prolonged,the percentage of the resting time in the quadrant of the platform and the frequency of acrossing the effective area of platform in the fifth day of space exploration experiment were significantly reduced of Morris water maze test,and visiting distance,duration and numbers in novel arm significantly increased of Y-maze test(P<0.05).2)Compared with group C,the total volume of white matter,total length of myelinated nerve fibers,total volume of myelinated nerve fibers and myelin sheath in the group PE were significantly reduced(P<0.05),the inner diameter and outer diameter of myelin sheath decreased significantly(P<0.05),and the inner perimeter,outer perimeter and inner and outer perimeter differences increased significantly(P<0.05).3)There was a correlation between behavioral test results and white matter ultrastructure measurement results.Conclusions:Maternal stress exposure during pregnancy could impair the cognitive function and white matter and its ultrastructure in the offspring,and there was a correlation between decreased cognitive function and white matter damages.展开更多
Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time (Bowen and Atwood, 2004; Grady, 2012). Aging-related...Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time (Bowen and Atwood, 2004; Grady, 2012). Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability (Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012). In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width (Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012). In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer's disease (Blatter et al., 1995; Tang et al.,展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
In the current landscape of endothelial cell isolation for building in vitro models of the blood-brain barrier,our work moves towards reproducing the features of the neurovascular unit to achieve glial compliance thro...In the current landscape of endothelial cell isolation for building in vitro models of the blood-brain barrier,our work moves towards reproducing the features of the neurovascular unit to achieve glial compliance through an innovative biomimetic coating technology for brain chronic implants.We hypothesized that the autologous origin of human brain mic rovascular endothelial cells(hBMECs)is the first requirement for the suitable coating to prevent the glial inflammato ry response trigge red by foreign neuroprosthetics.Therefo re,this study established a new procedure to preserve the in vitro viability of hBMECs isolated from gray and white matter specimens taken from neurosurge ry patients.Culturing adult hBMECs is generally considered a challenging task due to the difficult survival ex vivo and progressive reduction in proliferation of these cells.The addition of 10 nMβ-estradiol 17-acetate to the hBMEC culture medium was found to be an essential and discriminating factor promoting adhesion and proliferation both after isolation and thawing,suppo rting the well-known protective role played by estrogens on microvessels.In particular,β-estradiol 17-acetate was critical for both freshly isolated and thawed female-derived hBMECs,while it was not necessary for freshly isolated male-derived hBMECs;however,it did countera ct the decay in the viability of the latter after thawing.The tumo r-free hBMECs were thus cultured for up to 2 months and their growth efficiency was assessed befo re and after two periods of cryopreservation.Des pite the thermal stress,the hBMECs remained viable and suitable for re-freezing and storage for several months.This approach increasing in vitro viability of hBMECs opens new perspectives for the use of cryopreserved autologous hBMECs as biomimetic therapeutic tools,offering the potential to avoid additional surgical sampling for each patient.展开更多
Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common ...Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function,and can therefore also be used to reflect whole-brain structural changes related to T2 DM.A total of 136 participants(64 men and 72 women,aged 55–86 years) were recruited for our study between January 2014 and December 2016.All participants underwent MRI and Mini-Mental State Examination assessment(including 42 healthy control,38 T2 DM without cognitive impairment,26 with cognitive impairment but without T2 DM,and 30 T2 DM with cognitive impairment participants).The total and sub-category brain atrophy and lesion index scores in patients with T2 DM with cognitive impairment were higher than those in healthy controls.Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2 DM patients with cognitive impairment and patients with T2 DM and cognitive impairment.After adjusting for age,the brain atrophy and lesion index retained its capacity to identify patients with T2 DM with cognitive impairment.These findings suggest that the brain atrophy and lesion index,based on T1-weighted and T2-weighted imaging,is of clinical value for identifying patients with T2 DM and cognitive impairment.Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2 DM that is complicated by cognitive impairment.This study was approved by the Medical Ethics Committee of University of South China(approval No.USC20131109003) on November 9,2013,and was retrospectively registered with the Chinese Clinical Trial Registry(registration No.Chi CTR1900024150) on June 27,2019.展开更多
It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we inves- tigated whether t...It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we inves- tigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+) The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were as- sessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)〈 I(+)P(-)〈 I(-)P(+)〈 I(+)P(+) (P〈0.0001). For the pa- tients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P〈0.0025, P〈0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.展开更多
As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementi...As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementia VCI.Early symptoms of non-dementia VCI are hidden and difficult to identify.About 50% of patients develop dementia.This article reviews the correlation between WMLs and VCI in terms of etiology,risk factors,pathogenesis and imaging manifestations.It provides scientific basis or ideas for clinical diagnosis and treatment for WMLs and VCI.展开更多
Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by c...Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.展开更多
Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained defic...Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.展开更多
We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. ...We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.展开更多
Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system.Over the last few decades,a great deal of attention has been...Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system.Over the last few decades,a great deal of attention has been focused on white matter as a potential therapeutic target,mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system,a cell type able to fully repair myelin damage,and to the development of advanced imaging techniques to visualize and measure white matter lesions.The combination of these two events has greatly increased the body of research into white matter alte rations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair,thus indirectly contributing to neuroprotection.This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system.Pivot conditions are discussed,specifically multiple scle rosis as a white matter disease;spinal cord injury,the acute lesion of a central nervous system component where white matter prevails over the gray matte r,and Alzheimer's disease,where the white matter was considered an ancilla ry component until recently.We first describe oligodendrocyte precursor cell biology and developmental myelination,and its regulation by thyroid hormones,then briefly describe white matter imaging techniques,which are providing information on white matter involvement in central nervous system lesions and degenerative diseases.Finally,we discuss pathological mechanisms which interfere with myelin repair in adulthood.展开更多
Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients ...Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions.Notably,immune cell nodular lesion(NL) was a conspicuous type of pathological change in HIV/SIV(simian immunodeficiency virus) infected brain before cART.Therefore,we used SIV infected brain to investigate the distribution of those NLs in gray and white matters.We found a significant higher number of NLs in white matter than that in gray matter.However,virus infection correlated with macrophage NLs but not with microglia NLs,especially in white matter.In addition,NLs interrupted white matter integrity more severely,since even tiny nodules could disconnect nerve fibers in white matter tracts.In the gray matter with dense myelinated axons,NLs obviously encroached those fibers;in the area of few myelinated axons,small nodules well co-localized with extracellular matrix between neurons.展开更多
Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is ...Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction(IUGR).Injury of all types can impact the motor and cognitive abilities of survivors.The mechanisms leading to disability are not completely understood.展开更多
Objective To evaluate the usefulness of diffusion tensor MR imaging in brain white matter diseases. Methods A combined conventional and diffusion tensor MRI were obtained from 10 multiple sclerosis ,10 multiple lacuna...Objective To evaluate the usefulness of diffusion tensor MR imaging in brain white matter diseases. Methods A combined conventional and diffusion tensor MRI were obtained from 10 multiple sclerosis ,10 multiple lacunar infarction,3 cysticercosis,1 angiitis ,1 morphinist and 10 healthy control volunteers. After obtaining mean diffusivity (D) and fractional anisotropy images and image coregistration, the correlations of the lesions and the white matter pathways were investigated. D and AI values were measured form four big lesions which can be seen in T2WI and compared to contralateral white matter. Also D and AI value of four different anatomic locations of normal appearing white matter regions were measured in all patients and controls. Results Whereas the lesions of infarction, cysticercosis and angiitis were in and outside the white matter pathways, all plaques of multiple sclerosis were inside the whit matter pathways. The brain white matter lesions by 1 morphinist were beside the lateral ventricle with big patchy appearance, which was partly inside white matter. For MS, D value was higher in lesions than control white matter. But for other diseases, D value could be seen higher or lower compared to healthy side. AI values were lower in all lesions. D value was higher and AI was lower in normal appearing brain white matter when comparing MS to other cases or healthy control volunteers. Conclusion Diffusion tensor MR images can determine the correlations of the lesions and brain white matter pathways. The changes of D and AI values can improve specificity in differential diagnoses though quantitatively analyzing the tissue damage in lesions and normal appearing brain white matter.展开更多
With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed...With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.展开更多
Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray ma...Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.展开更多
Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract c...Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract connections may impose on neuronal signal traffic. We propose a model developed by Copelli and Kinouchi (l.c.) for a different purpose to safeguard signal transmission for brain connectivity by ensuring dynamic adaptation of signal reception to a wide frequency range of traffic flow over connecting fiber tracts. Gap junction connectivity would confer to neuronal groups the capacity of acting as collectives for dynamical adaptability to impinging neural traffic thereby forestalling traffic congestion and overload. It is suggested that applying this model to signal reception in brain connectivity would deliver the required functionality as a collective achievement of the interrelations between neurons and gap junctions, the latter regulated by glia.展开更多
文摘Background:White matter lesion(WML)is common in aging brain and is associated with cognitive impairment and dementia.However,recent studies reported an association between patent foramen ovale(PFO)and WML in migraineurs,especially in young,middle-aged migraineurs.Our retrospective,case-control study aims to describe the clinical characteristics of WML in this population and to explore potential risk factors.Methods:226 patients with migraine and PFO were consecutively initially screened.Relevant factors were selected by the least absolute shrinkage and selection operator(LASSO)regression and multivariable logistic regression model.A Nomogram was employed to visualize the prediction model conveniently.The discrimination and calibration abilities were evaluated using the Receiver Operating Characteristic(ROC)curve,the Hosmer-Lemeshow test,and calibration curves.Results:One hundred and nineteen participants were ultimately enrolled in our study,with a median age of 36.9±12.7 years and 80.7%of females.Brain magnetic resonance imaging MRI showed 67(56.3%)patients had WML,whereas 52(43.7%)patients were categorized into the non-WML group.LASSO regression screened out potential variables and subsequent multivariate analysisfinally identified age,mean platelet volume,andfibri-nogen(FIB)as independent predictive factors of WML.The area under the ROC curve(AUC)was 0.807.Hos-mer-Lemeshow test and calibration curve verified a consistency between the predicted and actual probability.Conclusion:The predictive nomogram established and validated in our study may assist clinicians in screening WML among young middle-aged migraineurs with PFO and developing individualized preventive and treatment strategies.
基金Shaanxi Province natural science basic research program (No.2023-JC-QN-0961)。
文摘Objective:To explore whether maternal stress exposure during pregnancy impairs cognitive function and white matter ultrastructure in offspring mice.Methods:The parent rats were divided into two groups:pressure exposure group(group PE)and control group(group C),and the positive date of vaginal smear of female SD rats was day 0 of gestation.Female mice in group PE were exposed to binding pressure(3 times/day)on day 14-20 of gestation for 45 min-1 h/time.Behavioral tests(Morris water maze and Y maze)were performed on 1-month-old offspring mice followed by cardiac perfusion of fixed brain specimens and placement in mixed fixative solution.The total volume of white matter,total length and volume of myelinated nerve fibers and total length and volume of myelin sheath were calculated using modern stereoscopic methods,and the inner and outer diameter and inner and outer circumference of the myelin sheath were analyzed.Results:1)Behavioral tests:compared with the group C,the average latency of the 3th and 4th day in the group PE were significantly prolonged,the percentage of the resting time in the quadrant of the platform and the frequency of acrossing the effective area of platform in the fifth day of space exploration experiment were significantly reduced of Morris water maze test,and visiting distance,duration and numbers in novel arm significantly increased of Y-maze test(P<0.05).2)Compared with group C,the total volume of white matter,total length of myelinated nerve fibers,total volume of myelinated nerve fibers and myelin sheath in the group PE were significantly reduced(P<0.05),the inner diameter and outer diameter of myelin sheath decreased significantly(P<0.05),and the inner perimeter,outer perimeter and inner and outer perimeter differences increased significantly(P<0.05).3)There was a correlation between behavioral test results and white matter ultrastructure measurement results.Conclusions:Maternal stress exposure during pregnancy could impair the cognitive function and white matter and its ultrastructure in the offspring,and there was a correlation between decreased cognitive function and white matter damages.
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF)funded by the Ministry of Education, Science and Technology, No. 2012R1A1B4003477
文摘Introduction Aging is the accumulation of multidimensional deterioration of process- ing of biological, psychological, and social changes with expansion over time (Bowen and Atwood, 2004; Grady, 2012). Aging-related changes are typically accompanied by decline in cognitive function, urinary control, sensory-motor function, and gait ability (Bradley et al., 1991; Bowen and Atwood, 2004; Hedden and Gabrieli, 2004; Grady, 2012; Moran et al., 2012). In addition, a number of studies have suggested changes in brain structure with normal aging, such as decrease in cortical thickness or increase in ventricular width (Blatter et al., 1995; Tang et al., 1997; Uylings and de Brabander, 2002; Preul et al., 2006; Apostolova et al., 2012). In particular, ventricular enlargement has been suggested as a structural biomarker for normal aging and progression of some illnesses, such as Alzheimer's disease (Blatter et al., 1995; Tang et al.,
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
基金supported by EnTimeMent H2020-FETPROACT-824160(to LF)。
文摘In the current landscape of endothelial cell isolation for building in vitro models of the blood-brain barrier,our work moves towards reproducing the features of the neurovascular unit to achieve glial compliance through an innovative biomimetic coating technology for brain chronic implants.We hypothesized that the autologous origin of human brain mic rovascular endothelial cells(hBMECs)is the first requirement for the suitable coating to prevent the glial inflammato ry response trigge red by foreign neuroprosthetics.Therefo re,this study established a new procedure to preserve the in vitro viability of hBMECs isolated from gray and white matter specimens taken from neurosurge ry patients.Culturing adult hBMECs is generally considered a challenging task due to the difficult survival ex vivo and progressive reduction in proliferation of these cells.The addition of 10 nMβ-estradiol 17-acetate to the hBMEC culture medium was found to be an essential and discriminating factor promoting adhesion and proliferation both after isolation and thawing,suppo rting the well-known protective role played by estrogens on microvessels.In particular,β-estradiol 17-acetate was critical for both freshly isolated and thawed female-derived hBMECs,while it was not necessary for freshly isolated male-derived hBMECs;however,it did countera ct the decay in the viability of the latter after thawing.The tumo r-free hBMECs were thus cultured for up to 2 months and their growth efficiency was assessed befo re and after two periods of cryopreservation.Des pite the thermal stress,the hBMECs remained viable and suitable for re-freezing and storage for several months.This approach increasing in vitro viability of hBMECs opens new perspectives for the use of cryopreserved autologous hBMECs as biomimetic therapeutic tools,offering the potential to avoid additional surgical sampling for each patient.
基金supported by the National Natural Science Foundation of China,No.81271538 (to SNP)345 Talent Project and the Natural Science Foundation of Liaoning Province of China,No.2019-ZD-0794 (to SNP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2017JJ2225 (to JCL),2018JJ2357 (to GHL)Hunan Provincial Science and Technology Innovation Program of China,No.2017SK50203 (to HZ)。
文摘Patients with type 2 diabetes mellitus(T2 DM) often have cognitive impairment and structural brain abnormalities.The magnetic resonance imaging(MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function,and can therefore also be used to reflect whole-brain structural changes related to T2 DM.A total of 136 participants(64 men and 72 women,aged 55–86 years) were recruited for our study between January 2014 and December 2016.All participants underwent MRI and Mini-Mental State Examination assessment(including 42 healthy control,38 T2 DM without cognitive impairment,26 with cognitive impairment but without T2 DM,and 30 T2 DM with cognitive impairment participants).The total and sub-category brain atrophy and lesion index scores in patients with T2 DM with cognitive impairment were higher than those in healthy controls.Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2 DM patients with cognitive impairment and patients with T2 DM and cognitive impairment.After adjusting for age,the brain atrophy and lesion index retained its capacity to identify patients with T2 DM with cognitive impairment.These findings suggest that the brain atrophy and lesion index,based on T1-weighted and T2-weighted imaging,is of clinical value for identifying patients with T2 DM and cognitive impairment.Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2 DM that is complicated by cognitive impairment.This study was approved by the Medical Ethics Committee of University of South China(approval No.USC20131109003) on November 9,2013,and was retrospectively registered with the Chinese Clinical Trial Registry(registration No.Chi CTR1900024150) on June 27,2019.
基金supported by the National Natural Science Foundation of China (No. 30970962)
文摘It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we inves- tigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+) The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were as- sessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)〈 I(+)P(-)〈 I(-)P(+)〈 I(+)P(+) (P〈0.0001). For the pa- tients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P〈0.0025, P〈0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.
文摘As the incidence of cerebrovascular disease increases,the incidence of white matter lesions (WMLs) and vascular cognitive impairment (VCI) also increases.Ischemic WMLs is directly related to VCI,especially non-dementia VCI.Early symptoms of non-dementia VCI are hidden and difficult to identify.About 50% of patients develop dementia.This article reviews the correlation between WMLs and VCI in terms of etiology,risk factors,pathogenesis and imaging manifestations.It provides scientific basis or ideas for clinical diagnosis and treatment for WMLs and VCI.
文摘Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.
文摘Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.
基金supported by the Project of Science and Technology Department of Jilin Province in China,No.20160101023JC
文摘We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe(superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe(postcentral and inferior parietal gyri), right temporal lobe(caudate nucleus), right occipital lobe(middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.
文摘Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system.Over the last few decades,a great deal of attention has been focused on white matter as a potential therapeutic target,mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system,a cell type able to fully repair myelin damage,and to the development of advanced imaging techniques to visualize and measure white matter lesions.The combination of these two events has greatly increased the body of research into white matter alte rations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair,thus indirectly contributing to neuroprotection.This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system.Pivot conditions are discussed,specifically multiple scle rosis as a white matter disease;spinal cord injury,the acute lesion of a central nervous system component where white matter prevails over the gray matte r,and Alzheimer's disease,where the white matter was considered an ancilla ry component until recently.We first describe oligodendrocyte precursor cell biology and developmental myelination,and its regulation by thyroid hormones,then briefly describe white matter imaging techniques,which are providing information on white matter involvement in central nervous system lesions and degenerative diseases.Finally,we discuss pathological mechanisms which interfere with myelin repair in adulthood.
基金supported by R01 NS063878,R01 NS077873 and P30 MH062261(to H.X.and H.S.F.)。
文摘Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions.Notably,immune cell nodular lesion(NL) was a conspicuous type of pathological change in HIV/SIV(simian immunodeficiency virus) infected brain before cART.Therefore,we used SIV infected brain to investigate the distribution of those NLs in gray and white matters.We found a significant higher number of NLs in white matter than that in gray matter.However,virus infection correlated with macrophage NLs but not with microglia NLs,especially in white matter.In addition,NLs interrupted white matter integrity more severely,since even tiny nodules could disconnect nerve fibers in white matter tracts.In the gray matter with dense myelinated axons,NLs obviously encroached those fibers;in the area of few myelinated axons,small nodules well co-localized with extracellular matrix between neurons.
文摘Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction(IUGR).Injury of all types can impact the motor and cognitive abilities of survivors.The mechanisms leading to disability are not completely understood.
文摘Objective To evaluate the usefulness of diffusion tensor MR imaging in brain white matter diseases. Methods A combined conventional and diffusion tensor MRI were obtained from 10 multiple sclerosis ,10 multiple lacunar infarction,3 cysticercosis,1 angiitis ,1 morphinist and 10 healthy control volunteers. After obtaining mean diffusivity (D) and fractional anisotropy images and image coregistration, the correlations of the lesions and the white matter pathways were investigated. D and AI values were measured form four big lesions which can be seen in T2WI and compared to contralateral white matter. Also D and AI value of four different anatomic locations of normal appearing white matter regions were measured in all patients and controls. Results Whereas the lesions of infarction, cysticercosis and angiitis were in and outside the white matter pathways, all plaques of multiple sclerosis were inside the whit matter pathways. The brain white matter lesions by 1 morphinist were beside the lateral ventricle with big patchy appearance, which was partly inside white matter. For MS, D value was higher in lesions than control white matter. But for other diseases, D value could be seen higher or lower compared to healthy side. AI values were lower in all lesions. D value was higher and AI was lower in normal appearing brain white matter when comparing MS to other cases or healthy control volunteers. Conclusion Diffusion tensor MR images can determine the correlations of the lesions and brain white matter pathways. The changes of D and AI values can improve specificity in differential diagnoses though quantitatively analyzing the tissue damage in lesions and normal appearing brain white matter.
基金supported by a grant from the Clinical Medicine Science and Technology Projects in Jiangsu Province of China,No.BL2014037a grant from the Changzhou City Science and Technology Support Plan in China,No.CE20165027+1 种基金a grant from the Changzhou Health Development Planning Commission Major Projects in China,No.ZD201515the Changzhou High-Level Health Personnel Training Project Funding
文摘With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.
基金supported by the National Natural Science Foundation of China,No.30960398,81260213the Forty-Seventh Batch of China Postdoctoral Science Foundation,No.20100470376
文摘Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.
文摘Brain connectivity is commonly studied in terms of causal interaction or statistical dependency between brain regions. In this analysis paper, we draw attention to the constraining effect the dynamics of fiber tract connections may impose on neuronal signal traffic. We propose a model developed by Copelli and Kinouchi (l.c.) for a different purpose to safeguard signal transmission for brain connectivity by ensuring dynamic adaptation of signal reception to a wide frequency range of traffic flow over connecting fiber tracts. Gap junction connectivity would confer to neuronal groups the capacity of acting as collectives for dynamical adaptability to impinging neural traffic thereby forestalling traffic congestion and overload. It is suggested that applying this model to signal reception in brain connectivity would deliver the required functionality as a collective achievement of the interrelations between neurons and gap junctions, the latter regulated by glia.