BACKGROUND Several studies have reported that the walking trail making test(WTMT)completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments.We hypothes...BACKGROUND Several studies have reported that the walking trail making test(WTMT)completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments.We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities(WMH).AIM To explore the performance in the WTMT in older people with WMH.METHODS In this single-center,observational study,25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age,gender,and educational level who were undergoing physical examination in our hospital during the same period served as the control group.The participants completed the WTMT-A and WTMT-B to obtain their gait parameters,including WTMT-A completion time,WTMT-B completion time,speed,step length,cadence,and stance phase percent.White matter lesions were scored according to the Fazekas scale.Multiple neuropsychological assessments were carried out to assess cognitive function.The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis.RESULTS Patients with WMH performed significantly worse on the choice reaction test(CRT)(0.51±0.09 s vs 0.44±0.06 s,P=0.007),verbal fluency test(VFT,14.2±2.75 vs 16.65±3.54,P=0.012),and digit symbol substitution test(16.00±2.75 vs 18.40±3.27,P=0.010)than participants in the control group.The WMH group also required significantly more time to complete the WTMT-A(93.00±10.76 s vs 70.55±11.28 s,P<0.001)and WTMT-B(109.72±12.26 s vs 82.85±7.90 s,P<0.001).WTMT-A completion time was positively correlated with CRT time(r=0.460,P=0.001),while WTMT-B completion time was negatively correlated with VFT(r=-0.391,P=0.008).On the WTMT-A,only speed was found to statistically differ between the WMH and control groups(0.803±0.096 vs 0.975±0.050 m/s,P<0.001),whereas on the WTMT-B,the WMH group exhibited a significantly lower speed(0.778±0.111 vs 0.970±0.053 m/s,P<0.001)and cadence(82.600±4.140 vs 85.500±5.020 steps/m,P=0.039),as well as a higher stance phase percentage(65.061±1.813%vs 63.513±2.465%,P=0.019)relative to controls.CONCLUSION Older adults with WMH showed obviously poorer WTMT performance.WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.展开更多
BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,wi...BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of suicide.In studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is sparse.Some researchers even mistakenly regard the signals generated by the WM as noise points.In fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations.The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.AIM To explore potential abnormalities in WM functional signals in adolescents with MDD.METHODS This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide inventory.In addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image data.The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC groups.Independent component analysis(ICA)was also used to evaluate the WM functional signal.Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.RESULTS Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel correction).The ICA results of WM overlapped with those of regional homogeneity.The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale(P=0.026,r=-0.32),and the right posterior corona radiata was also negatively correlated with the MINI suicide scale(P=0.047,r=-0.288).CONCLUSION Adolescents with MDD involves changes in WM functional signals,and these differences in brain regions may increase the risk of suicide.展开更多
Objective Exosomal long noncoding RNAs(lnc RNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lnc RNAs in white matter hyperintensiti...Objective Exosomal long noncoding RNAs(lnc RNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lnc RNAs in white matter hyperintensities(WMH).Methods We used high-throughput sequencing to determine the differential expression(DE) profiles of lnc RNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using q RT-PCR. The diagnostic potential of candidate exosomal lnc RNAs was proven by binary logistic analysis and receiver operating characteristic(ROC) curves. The diagnostic value of DE exo-lnc RNAs was determined by the area under the curve(AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lnc RNAs in the subgroup was evaluated.Results In our results, four DE exo-lnc RNAs were identified, and ROC curve analysis revealed that exolnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.Conclusion Plasma exosomal lnc RNAs have potential diagnostic value in WMH. Moreover, exolnc_011797 is considered to be a predictor of the severity and location of WMH.展开更多
A mathematical model was developed to predict the risk of having a stroke as a person ages. The age component was derived from the concept that the change in risk of stroke with age is a function of the current risk o...A mathematical model was developed to predict the risk of having a stroke as a person ages. The age component was derived from the concept that the change in risk of stroke with age is a function of the current risk of developing a stroke. This equation modeled the trend with age reported in the literature for two different data sets with R<sup>2</sup> values of 0.97 or better for both men and women. A second equation of a similar nature was developed to predict the accumulation of white matter hyperintensities, WMH, as a person ages. It appears that each equation includes a set of common risk factors. This set of common risk factors allows an individual’s risk for stroke to be based on measured WMH. A third equation links WMH with the risk of developing a stroke. This equation allows an individual to use measured WMH from brain scans to predict the future risk of developing a stroke. In theory, a person with a relatively high measurement of WMH can project future risk for stroke with age and use counter measures such as exercise and medications to keep other risk factors low as a person continues to age.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
Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high...Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.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
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
Carnosine is a dipeptide that scavenges free radicals,inhibits inflammation in the central nervous system,and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions.Th...Carnosine is a dipeptide that scavenges free radicals,inhibits inflammation in the central nervous system,and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions.Therefore,we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury.White matter damage was induced by right unilateral common carotid artery occlusion in mice.The animals were treated with 200,500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury.Then,37 days later,Klüver-Barrera staining,toluidine blue staining and immunofluorescence staining were performed.Carnosine(200,500 mg/kg) substantially reduced damage to the white matter in the corpus callosum,internal capsule and optic tract,and it rescued expression of myelin basic protein,and alleviated the loss of oligodendrocytes.However,carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses.These findings show that carnosine,at a particular dose range,protects against white matter damage caused by chronic cerebral ischemia in mice,likely by reducing oligodendroglial cell loss.展开更多
Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularize...Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.展开更多
Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological ba...Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.展开更多
The spinal cord is composed of gray matter and white matter.It is well known that the properties of these two tissues differ considerably.Spinal diseases often present with symptoms that are caused by spinal cord comp...The spinal cord is composed of gray matter and white matter.It is well known that the properties of these two tissues differ considerably.Spinal diseases often present with symptoms that are caused by spinal cord compression.Understanding the mechanical properties of gray and white matter would allow us to gain a deep understanding of the injuries caused to the spinal cord and provide information on the pathological changes to these distinct tissues in several disorders.Previous studies have reported on the physical properties of gray and white matter,however,these were focused on longitudinal tension tests.Little is known about the differences between gray and white matter in terms of their response to compression.We therefore performed mechanical compression test of the gray and white matter of spinal cords harvested from cows and analyzed the differences between them in response to compression.We conducted compression testing of gray matter and white matter to detect possible differences in the collapse rate.We found that increased compression(especially more than 50%compression)resulted in more severe injuries to both the gray and white matter.The present results on the mechanical differences between gray and white matter in response to compression will be useful when interpreting findings from medical imaging in patients with spinal conditions.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
In spinal cord injuries,external forces from various directions occur at various velocities.Therefore,it is important to physically evaluate whether the spinal cord is susceptible to damage and an increase in internal...In spinal cord injuries,external forces from various directions occur at various velocities.Therefore,it is important to physically evaluate whether the spinal cord is susceptible to damage and an increase in internal stress for external forces.We hypothesized that the spinal cord has mechanical features that vary under stress depending on the direction and velocity of injury.However,it is difficult to perform experiment because the spinal cord is very soft.There are no reports on the effects of multiple external forces.In this study,we used bovine spinal cord white matter to test and analyze the anisotropy and velocity dependence of the spinal cord.Tensile-vertical,tensile-parallel,shear-vertical,and shear-parallel tests were performed on the white matter in the fibrous direction(cranial to caudal).Strain rate in the experiment was 0.1,1,10,and 100/s.We calculated the Young’s modulus of the spinal cord.Results of the tensile and shear tests revealed that stress tended to increase when external forces were applied parallel to the direction of axon fibers,such as in tensile-vertical and shear-vertical tests.However,external forces those tear against the fibrous direction and vertically,such as in tensile-parallel and shear-parallel tests,were less likely to increase stress even with increased velocity.We found that the spinal cord was prone to external forces,especially in the direction of the fibers,and to be under increased stress levels when the velocity of external forces increased.From these results,we confirmed that the spinal cord has velocity dependence and anisotropy.The Institutional Animal Care and Use Committee of Yamaguchi University waived the requirement for ethical approval.展开更多
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hype...Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.展开更多
The corticospinal tract(CST)is a major neural tract for motor function in the human brain.In addition,CST is mainly concerned with execution of movement of the hand(Jang,2014).However,few studies are reported on the m...The corticospinal tract(CST)is a major neural tract for motor function in the human brain.In addition,CST is mainly concerned with execution of movement of the hand(Jang,2014).However,few studies are reported on the mechanism underlying CST recovery after traumatic brain injury(Seo and Jang,2015).In this study,we report on a case that showed recovery of an injured CST by traumatic展开更多
With the increasing application of regenerative medicine in vivo,non-invasive and accurate methods for estimating the white matter axons in neuronal tissue have become increasingly important.As a non-invasive method f...With the increasing application of regenerative medicine in vivo,non-invasive and accurate methods for estimating the white matter axons in neuronal tissue have become increasingly important.As a non-invasive method for patients,magnetic resonance(MR)imaging has demonstrated potential as a promising tool for evaluating axons in vivo.In particular,diffusion-weighted MR imaging(d MRI)and its applications,such as white matter tractography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
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
Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment(Jokinen et al.,2011),declines in global functionality(Inzitari et al.,2009),and even death(Debette and M...Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment(Jokinen et al.,2011),declines in global functionality(Inzitari et al.,2009),and even death(Debette and Markus,2010).Twenty years ago,estimations of the clinical incidence of cerebral microvascular disease approached 11 million per展开更多
基金Supported by The Wu Jieping Medical Foundation,No.320.6750.18456.
文摘BACKGROUND Several studies have reported that the walking trail making test(WTMT)completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments.We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities(WMH).AIM To explore the performance in the WTMT in older people with WMH.METHODS In this single-center,observational study,25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age,gender,and educational level who were undergoing physical examination in our hospital during the same period served as the control group.The participants completed the WTMT-A and WTMT-B to obtain their gait parameters,including WTMT-A completion time,WTMT-B completion time,speed,step length,cadence,and stance phase percent.White matter lesions were scored according to the Fazekas scale.Multiple neuropsychological assessments were carried out to assess cognitive function.The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis.RESULTS Patients with WMH performed significantly worse on the choice reaction test(CRT)(0.51±0.09 s vs 0.44±0.06 s,P=0.007),verbal fluency test(VFT,14.2±2.75 vs 16.65±3.54,P=0.012),and digit symbol substitution test(16.00±2.75 vs 18.40±3.27,P=0.010)than participants in the control group.The WMH group also required significantly more time to complete the WTMT-A(93.00±10.76 s vs 70.55±11.28 s,P<0.001)and WTMT-B(109.72±12.26 s vs 82.85±7.90 s,P<0.001).WTMT-A completion time was positively correlated with CRT time(r=0.460,P=0.001),while WTMT-B completion time was negatively correlated with VFT(r=-0.391,P=0.008).On the WTMT-A,only speed was found to statistically differ between the WMH and control groups(0.803±0.096 vs 0.975±0.050 m/s,P<0.001),whereas on the WTMT-B,the WMH group exhibited a significantly lower speed(0.778±0.111 vs 0.970±0.053 m/s,P<0.001)and cadence(82.600±4.140 vs 85.500±5.020 steps/m,P=0.039),as well as a higher stance phase percentage(65.061±1.813%vs 63.513±2.465%,P=0.019)relative to controls.CONCLUSION Older adults with WMH showed obviously poorer WTMT performance.WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.
基金Supported by the Suzhou Clinical Medical Center for Mood Disorders,No.Szlcyxzx202109Jiangsu Provincial Department of Science and Technology for Social Development-General Project,No.BE2022735.
文摘BACKGROUND Major depression disorder(MDD)constitutes a significant mental health concern.Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults,with a corresponding increased risk of suicide.In studying brain dysfunction associated with MDD in adolescents,research on brain white matter(WM)is sparse.Some researchers even mistakenly regard the signals generated by the WM as noise points.In fact,studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations.The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear.AIM To explore potential abnormalities in WM functional signals in adolescents with MDD.METHODS This study involved 48 adolescent patients with MDD and 31 healthy controls(HC).All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview(MINI)suicide inventory.In addition,a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects'image data.The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations(fALFF)and regional homogeneity,followed by a two-sample t-test between the MDD and HC groups.Independent component analysis(ICA)was also used to evaluate the WM functional signal.Pearson’s correlation was performed to assess the relationship between statistical test results and clinical scales.RESULTS Compared to HC,individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body,left posterior limb of the internal capsule,right superior corona radiata,and bilateral posterior corona radiata[P<0.001,family-wise error(FWE)voxel correction].The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata,and decreased in the left superior longitudinal fasciculus(P<0.001,FWE voxel correction).The ICA results of WM overlapped with those of regional homogeneity.The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale(P=0.026,r=-0.32),and the right posterior corona radiata was also negatively correlated with the MINI suicide scale(P=0.047,r=-0.288).CONCLUSION Adolescents with MDD involves changes in WM functional signals,and these differences in brain regions may increase the risk of suicide.
文摘Objective Exosomal long noncoding RNAs(lnc RNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lnc RNAs in white matter hyperintensities(WMH).Methods We used high-throughput sequencing to determine the differential expression(DE) profiles of lnc RNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using q RT-PCR. The diagnostic potential of candidate exosomal lnc RNAs was proven by binary logistic analysis and receiver operating characteristic(ROC) curves. The diagnostic value of DE exo-lnc RNAs was determined by the area under the curve(AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lnc RNAs in the subgroup was evaluated.Results In our results, four DE exo-lnc RNAs were identified, and ROC curve analysis revealed that exolnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.Conclusion Plasma exosomal lnc RNAs have potential diagnostic value in WMH. Moreover, exolnc_011797 is considered to be a predictor of the severity and location of WMH.
文摘A mathematical model was developed to predict the risk of having a stroke as a person ages. The age component was derived from the concept that the change in risk of stroke with age is a function of the current risk of developing a stroke. This equation modeled the trend with age reported in the literature for two different data sets with R<sup>2</sup> values of 0.97 or better for both men and women. A second equation of a similar nature was developed to predict the accumulation of white matter hyperintensities, WMH, as a person ages. It appears that each equation includes a set of common risk factors. This set of common risk factors allows an individual’s risk for stroke to be based on measured WMH. A third equation links WMH with the risk of developing a stroke. This equation allows an individual to use measured WMH from brain scans to predict the future risk of developing a stroke. In theory, a person with a relatively high measurement of WMH can project future risk for stroke with age and use counter measures such as exercise and medications to keep other risk factors low as a person continues to age.
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This work was supported by the National Research Foundation of Korea(NRF)grants funded by the Korea government(MSIT,Ministry of Science and ICT)(NRF-2018M3A9E8023853(to JYC)NRF-2018R1C1B6006145(to JYC)NRF-2018R1A2A1A05020292(to BGK)and NRF-2019R1A5A2026045(to JYC and BGK).
文摘Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.
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 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funded by the National Natural Science Foundation of China,No.81402904the Foundation of Shanghai Jiao Tong University School of Medicine,No.13XJ22001+1 种基金the Foundation of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.13YJ11a grant from the Science and Technology Commission of Shanghai Municipality of China,No.13ZR1426900,15411963900
文摘Carnosine is a dipeptide that scavenges free radicals,inhibits inflammation in the central nervous system,and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions.Therefore,we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury.White matter damage was induced by right unilateral common carotid artery occlusion in mice.The animals were treated with 200,500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury.Then,37 days later,Klüver-Barrera staining,toluidine blue staining and immunofluorescence staining were performed.Carnosine(200,500 mg/kg) substantially reduced damage to the white matter in the corpus callosum,internal capsule and optic tract,and it rescued expression of myelin basic protein,and alleviated the loss of oligodendrocytes.However,carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses.These findings show that carnosine,at a particular dose range,protects against white matter damage caused by chronic cerebral ischemia in mice,likely by reducing oligodendroglial cell loss.
基金supported by grants from the National Key R&D Program of China,No.2017YFA0104704(to BQL)the Young Elite Scientist Sponsorship Program(YESS)by China Association for Science and Technology(CAST),No.2018QNRC001(to BQL)+1 种基金the Fundamental Research Funds for the Central Universities,China,No.18ykpy38(to BQL)the National Natural Science Foundation of China,Nos.81971157(to BQL),81891003(to YSZ).
文摘Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.
文摘Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.
基金supported by JSPS KAKENHI(No.JP 15K20002)Yamaguchi University School of Medicine Affiliated Hospital:Translational Promotion Grant and President of Yamaguchi University Strategic Expenses:Young Researcher Support Project(all to NN)
文摘The spinal cord is composed of gray matter and white matter.It is well known that the properties of these two tissues differ considerably.Spinal diseases often present with symptoms that are caused by spinal cord compression.Understanding the mechanical properties of gray and white matter would allow us to gain a deep understanding of the injuries caused to the spinal cord and provide information on the pathological changes to these distinct tissues in several disorders.Previous studies have reported on the physical properties of gray and white matter,however,these were focused on longitudinal tension tests.Little is known about the differences between gray and white matter in terms of their response to compression.We therefore performed mechanical compression test of the gray and white matter of spinal cords harvested from cows and analyzed the differences between them in response to compression.We conducted compression testing of gray matter and white matter to detect possible differences in the collapse rate.We found that increased compression(especially more than 50%compression)resulted in more severe injuries to both the gray and white matter.The present results on the mechanical differences between gray and white matter in response to compression will be useful when interpreting findings from medical imaging in patients with spinal conditions.
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.
基金This work was supported by the Japan Society for the Promotion of Science(KARENHI grant number JP 15K20002)by the Yamaguchi University Hospital(a translational promotion grant).
文摘In spinal cord injuries,external forces from various directions occur at various velocities.Therefore,it is important to physically evaluate whether the spinal cord is susceptible to damage and an increase in internal stress for external forces.We hypothesized that the spinal cord has mechanical features that vary under stress depending on the direction and velocity of injury.However,it is difficult to perform experiment because the spinal cord is very soft.There are no reports on the effects of multiple external forces.In this study,we used bovine spinal cord white matter to test and analyze the anisotropy and velocity dependence of the spinal cord.Tensile-vertical,tensile-parallel,shear-vertical,and shear-parallel tests were performed on the white matter in the fibrous direction(cranial to caudal).Strain rate in the experiment was 0.1,1,10,and 100/s.We calculated the Young’s modulus of the spinal cord.Results of the tensile and shear tests revealed that stress tended to increase when external forces were applied parallel to the direction of axon fibers,such as in tensile-vertical and shear-vertical tests.However,external forces those tear against the fibrous direction and vertically,such as in tensile-parallel and shear-parallel tests,were less likely to increase stress even with increased velocity.We found that the spinal cord was prone to external forces,especially in the direction of the fibers,and to be under increased stress levels when the velocity of external forces increased.From these results,we confirmed that the spinal cord has velocity dependence and anisotropy.The Institutional Animal Care and Use Committee of Yamaguchi University waived the requirement for ethical approval.
基金This work was supported by National Natural Science Foundation of China(Grants No.81873727 and 82171196).
文摘Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.
基金supported by the National Research Foundation(NRF) of Korea Grant funded by the Korean Government(MSIP)(No.2015R1A2A2A01004073)
文摘The corticospinal tract(CST)is a major neural tract for motor function in the human brain.In addition,CST is mainly concerned with execution of movement of the hand(Jang,2014).However,few studies are reported on the mechanism underlying CST recovery after traumatic brain injury(Seo and Jang,2015).In this study,we report on a case that showed recovery of an injured CST by traumatic
基金supported by JSPS KAKENHI Grant Number JP16H06280Grant-in-Aid for Scientific Research on Innovative Areas-Resource and technical support platforms for promoting research‘Advanced Bioimaging Support’the Im PACT Program of Council for Science,Technology and Innovation(Cabinet Office,Government of Japan)
文摘With the increasing application of regenerative medicine in vivo,non-invasive and accurate methods for estimating the white matter axons in neuronal tissue have become increasingly important.As a non-invasive method for patients,magnetic resonance(MR)imaging has demonstrated potential as a promising tool for evaluating axons in vivo.In particular,diffusion-weighted MR imaging(d MRI)and its applications,such as white matter tractography
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support from the Larry L.Hillblom Foundation (GX)NIH NS083740 (JDH)the United States Department of Veterans Affairs Greater Los Angeles Healthcare System (JDH)
文摘Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment(Jokinen et al.,2011),declines in global functionality(Inzitari et al.,2009),and even death(Debette and Markus,2010).Twenty years ago,estimations of the clinical incidence of cerebral microvascular disease approached 11 million per
