Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cogniti...Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.展开更多
Objective: Vacuolating megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently described syndrome with autosomal recessive mode of inheritance. Its possible gene was located on chromosomal 22q ...Objective: Vacuolating megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently described syndrome with autosomal recessive mode of inheritance. Its possible gene was located on chromosomal 22q tel with 3-cM. The purpose of this study was to narrow down the genetical distance on chromosomal 22q tel with MLC. Methods: Thirty-nine MLC patients in 33 families were collected,and the linkage analysis and haplotype analysis of twelve informative families were done, using seven microsatellite markers and four SNP markers. Results: The maximum tow-point LOD score for marker 355c18 was 6.65 at recombination fraction 0.02. The haplotype analysis narrowed down the critical region of MLC to 250 kb on chromosomal 22q tel. Conclusion: One of the causing genes of MLC was located on chromosomal 22q tel with 250 kb. Four candidate genes were considered. The heterogeneity of one informative family indicated possible existence of a second locus for MLC.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
The corticospinal tract （CST） is a neural tract responsible for motor function in the human brain. It is mainly related to hand movements （Iang, 2014）. Therefore, recovery of an injured CST contributes to good rec...The corticospinal tract （CST） is a neural tract responsible for motor function in the human brain. It is mainly related to hand movements （Iang, 2014）. Therefore, recovery of an injured CST contributes to good recovery in stroke patients and a thorough knowledge of the recovery mechanism regarding an injured CST is required for successful brain rehabilitation.展开更多
The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoenceph...The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities.展开更多
The corticospinal tract （CST） is a major neural tract for mo- tor function in the human brain. In addition, CST is mainly concerned with execution of movement of the hand （Jang, 2014）. However, few studies are rep...The corticospinal tract （CST） is a major neural tract for mo- tor 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 mecha- nism 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 axonal injury （TAI） at subcortical white matter, as detected on fol- low-up diffusion tensor tractography （DTT）.展开更多
Here we review a new variety of leukoencephalopathy with infantile megalencephaly and discrepant clinical course (MLC, MIM: 604004). These children had megalencephaly in the first year of life, with or without mild de...Here we review a new variety of leukoencephalopathy with infantile megalencephaly and discrepant clinical course (MLC, MIM: 604004). These children had megalencephaly in the first year of life, with or without mild delay of motor function and/or seizures. After a few years, motor handicap was slowly progressive with unsteady gait, serious cerebellar ataxia and mild plasticity. Eventually most of patients were confined to a wheelchair. Meanwhile mental development was relatively preserved, although the learning problems was increased from the midway of elementary school. Most of patients had tonic-clonic seizure and some might advance to status epilepticus. Antiepileptic drugs may effectively control seizure. The disorders of known metabolic defects were excluded. Neurophysiological examination showed that EEG had interictal epileptic discharges on the generalized slow wave background in most patients. The cerebral white matter had diffuse abnormality, with swelling of white matter, and cysts in the frontoparietal and anterior-temporal lobes on MRI examination. Some central white matter structures were spared, such as corpus callosum. The severity of lesions on MRI is inconsistent with the clinical signs. Pathogenesis of this disease was unknown. The pathological findings found a spongiform leukoencephalopathy due to myelin splitting and intramyelinic vacuole formation but without myelin loss. This disease had probably an autosomal recessive inheritance. The gene KIAA027 on 22qtel was responsible for MLC.展开更多
Objective: To investigate the association of ischaemic and haemorrhagic strokes with the site of subcortical focal cerebrovascular injuries with affective, behavioural and cognitive dysfunctions in the acute phase and...Objective: To investigate the association of ischaemic and haemorrhagic strokes with the site of subcortical focal cerebrovascular injuries with affective, behavioural and cognitive dysfunctions in the acute phase and after three months. Sample: 58 patients with focal cerebrovascular injuries;mean age 61.5 ± 13.5, 72.4% male. Control group: 20 healthy subjects, mean age 67.1 ± 7.6, 50% male. Results: Significant differences were observed (p = 0.006) between the acute phase and three months later on the apathy items of the Neuropsychiatric Inventory (NPI) in patients with subcortical stroke. Significant differences were also observed on the affective scale of the BRMS (p = 0.004), the behaviour scale of the Maudsley Obsessive-Compulsive Inventory (MOCI) (p = 0.000), and on the Mini Mental State Examination (MMSE) (p = 0.006). No significant differences were observed on the Hamilton Rating Scale-Depression (HRSM) (p = 0.101). Significant differences were found according to the infarct type: patients with haemorrhagic lesions had higher raw scores on the HRS-D than those with ischaemic lesions (p = 0.024). Conclusions: The performance of patients with subcortical stroke on affective, behavioural and cognitive scales improves after three months. Patients with haemorrhagic lesions are more likely to be depressive than those with ischaemic lesions.展开更多
According to the proposed hypothesis, graphic characters trigger the subcortical visual route. The reaction discussed is very weak. Yet, its very existence has an unusual importance: characters and (occluded) venomous...According to the proposed hypothesis, graphic characters trigger the subcortical visual route. The reaction discussed is very weak. Yet, its very existence has an unusual importance: characters and (occluded) venomous snakeskin patterns reveal themselves as conflatable. Furthermore, following tractogra<span><span><span style="font-family:;" "="">- </span></span></span><span><span><span style="font-family:;" "="">phic research, a functional segregation of the subcortical pathway is to be <span>presupposed. Thus, there can’t be a later dissociation of two stimuli pre</span>viously associated. The outc</span></span></span><span><span><span style="font-family:;" "="">omes of lecture will gradually appear probabilistically <span>(much) more peaceful than encountering a venomous snake, though, and</span> thus a continuous lessening of the reaction is expectable. Here, on one hand, it is relevant that the subcortical visual pathway goes to the amygdala. The reactions we describe tap into goal-oriented processes, and they will do that un<span>fettered. On the other hand, in the case of characters, since the beginning,</span> fear has been converted into appetition to a great degree. This process should be fostered in the presence of light. In this way, luminosity might become a conditioned stimulus for attraction. In this case, a Pavlovian addiction for light <span>will foster, yet also—from the point of view of reward fee</span>ling—counterbalance the lessening of the stimulation elicited by characters. The addiction we refer to is one towards light accompanied by graphic signs. Yet, as opposed to the case of the luminous medium, the attention captured by the later ones taken for themselves is continuously reduced.</span></span></span>展开更多
Objective:We investigated changes in cortico–subcortical spatiotemporal dynamics to explore the treatment mechanisms oftranscranial alternating current stimulation(tACS)in patientswith Parkinson’s disease(PD).Method...Objective:We investigated changes in cortico–subcortical spatiotemporal dynamics to explore the treatment mechanisms oftranscranial alternating current stimulation(tACS)in patientswith Parkinson’s disease(PD).Methods:Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 20 patients with PD and 20 normal controls(NC).Each patient with PD received successivemultidisciplinary intensive rehabilitation treatment and tACStreatment over a one-year interval.Individual functional brain network mapping and co-activation pattern(CAP)analysis were performed to characterize cortico–subcortical dynamics.Results:The same tACS electrode placement stimulated different proportions of functional brain networks across the participants.CAP analysis revealed that the visual network,attentional network,and default mode network co-activated with the thalamus,accumbens,and amygdala,respectively.The pattern characterized by thede-activation of the visual network and the activation of the thalamus showed a significantly low amplitude in the patients with PD than inNCs,and this amplitude increased after tACS treatment.Furthermore,the co-occurrence of cortico–subcortical CAPs was significantly higherin patients with PD than in NCs and decreased after tACS treatment.Conclusions:This study investigated cortico–subcortical spatiotemporaldynamics in patients with PD and further revealed the tACS treatmentmechanism.These findings contribute to understanding cortico–subcortical dynamics and exploring noninvasive neuromodulationtargets of cortico–subcortical circuits in brain diseases,such as PD,Alzheimer’s disease,and depression.展开更多
Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific...Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific biomarkers.Extensive damage to the white matter tracts,which connect the cortical and subcortical regions,has been shown in subcortical VCI(SVCI),the most common subtype of VCI that is caused by small vessel disease.Two specific MRI sequences,including diffusion tensor imaging(DTI)and functional MRI(fMRI),have emerged as useful tools for identifying subtle white matter changes and the intrinsic connectivity between distinct cortical regions.This review describes the advantages of these two modalities in SVCI research and the current DTI and fMRI findings on SVCI.Using DTI technique,a variety of studies found that white matter microstructural damages in the anterior and superior areas are more specific to SVCI.Similarly,functional brain abnormalities detected by fMRI have also been mainly shown in anterior brain areas in SVCI.The characteristic distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical loop that results in cognitive impairments in particular domains,which further confirms the‘disconnection syndrome’hypothesis.In addition,another MRI technique,arterial spin labelling(ASL),has been used to describe the disconnection patterns in a variety of conditions by measuring cerebral blood flow.The role of the ASL technique in SVCI research is also assessed.Finally,the review proposes the application of multimodality fusion in the investigation of SVCI pathogenesis.展开更多
Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of t...Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.展开更多
Subcortical vascular mild cognitive impairment(svMCI)is a common prodromal stage of vascular dementia.Although mounting evidence has suggested abnormalities in several single brain network metrics,few studies have exp...Subcortical vascular mild cognitive impairment(svMCI)is a common prodromal stage of vascular dementia.Although mounting evidence has suggested abnormalities in several single brain network metrics,few studies have explored the consistency between functional and structural connectivity networks in svMCI.Here,we constructed such networks using resting-state f MRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls.The functional networks were then parcellated into topological modules,corresponding to several well-defined functional domains.The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level(whole brain and modular level).We found no significant intergroup differences in the functional–structural coupling within the whole brain;however,there was significantly increased functional–structural coupling within the dorsal attention module and decreased functional–structural coupling within the ventral attention module in the svMCI group.In addition,the svMCI patients demonstrated decreased intramodular connectivity strength in the visual,somatomotor,and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network,mainly linking the visual,somatomotor,dorsal attention,ventral attention,and frontoparietal control modules.There was no significant correlation between the altered module-level functional–structural coupling and cognitive performance in patients with svMCI.These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.展开更多
Background： Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL） is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imag...Background： Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL） is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography （EDI-OCT） to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging （MPRI） findings. Methods： Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First ttospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microblecds were evaluated. All patients and controls underwent EDI-OCT to measure subtbveal choroidal thickness （SFCT）, inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner （AVRin） and outer diameters （AVRout）. The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman＇s correlation was used to investigmc the correlation between retinal vessel changes and MRI lesions. Results： In CADASI L patients, mean SFCT （268.37 ± 46.50 μm） and mean arterial inner diameter （93.46 ± 9.70 gin） were signilicantly lower than that in controls （P 〈 0.00 ）, P = 0.048, respectively）. Mean arterial outer diameter （ 131.74 ± 10.87 μm）, venous inner （ 128.99 ± 13.62 μm） and outer diameter （ 164.82 ±14.77 μm）, and mean arterial （ 19.13 ±1.85 μm） and venous （ 17.91 ±2.76 μm） wall thickness were significantly higher than that in controls （P = 0.023, P 0.004, P 〈 0.001, P 〈 0.001, respectively）. Arterial inner diameter （r= - 0.39, P 0.044）] AVRin （r -0.65, P 〈 0.001）, and AVR,, （r =0.56, P - 0.002） showed a negative correlation with the number of small infarcts. Venous inner diameter （rs=0.46, P= 0.016） showed a positive correlation with the number of small infarcts. Venous inner diameter （r 0.59, P = 0.002）, outer diameter （rs=0.47, P= 0.017）, showed a positive correlation with the number of cerebral microbleeds （CM Bs）. AVRin （r =0.52, P = 0.007） and AVRout （r = -0.40, P =0.048） showed a negative correlation with the number of CMBs. Conclusions： Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might bc a useful evaluation tool for CADASIL patients.展开更多
Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclea...Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.展开更多
Background Megalencephalic leukoencephalopathy with subcortical cysts(MLC)is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inherit...Background Megalencephalic leukoencephalopathy with subcortical cysts(MLC)is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inheritance and a different prognosis,characterized by macrocephaly,delayed motor and cognitive development,and bilateral abnormal signals in cerebral white matter(WM)with or without cysts on magnetic resonance imaging(MRI).This study aimed to reveal the clinical and genetic features of MLC patients with GLIALCAM mutations and to explore the brain pathological characteristics and prognosis of mouse models with different modes of inheritance.Methods Clinical information and peripheral venous blood were collected from six families.Genetic analysis was performed by Sanger sequencing of GLIALCAM.Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mouse models were generated based on mutations from patients(c.274C>T(p.Arg92Trp)(c.203A>T(p.Lys68Met),and c.395C>A(p.Thr132Asn))).Brain pathologies of the mouse models at different time points were analyzed.Results Six patients were clinically diagnosed with MLC.Of the six patients,five(Pt1-Pt5)presented with a heterozygous mutation in GLIALCAM(c.274C>T(p.Arg92Trp)or c.275G>C(p.Arg92Pro))and were diagnosed with MLC2B;the remaining patient(Pt6)with two compound heterozygous mutations in GLIALCAM(c.203A>T(p.Lys68Met)and c.395C>A(p.Thr132Asn))was diagnosed with MLC2A.The mutation c.275C>G(p.Arg92Pro)has not been reported before.Clinical manifestations of the patient with MLC2A(Pt6)progressed with regression,whereas the course of the five MLC2B patients remained stable or improved.The Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mouse models showed vacuolization in the anterior commissural WM at 1 month of age and vacuolization in the cerebellar WM at 3 and 6 months,respectively.At 9 months,the vacuolization of the GlialcamiLys68Met/Thr132Asn mouse model was heavier than that of the Glialcam^(Arg92Trp/+)mouse model.Decreased expression of Glialcam in Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mice may contribute to the vacuolization.Conclusions Clinical and genetic characterization of patients with MLC and GLIALCAM mutations revealed a novel mutation,expanding the spectrum of GLIALCAM mutations.The first Glialcam mouse model with autosomal recessive inheritance and a new Glialcam mouse model with autosomal dominant inheritance were generated.The two mouse models with different modes of inheritance showed different degrees of brain pathological features,which were consistent with the patients'phenotype and further confirmed the pathogenicity of the corresponding mutations.展开更多
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), is the most common cause of inherited cerebral small vessel disease, inherited stroke and inherited vascular dement...Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), is the most common cause of inherited cerebral small vessel disease, inherited stroke and inherited vascular dementia. It is not infrequent for CADASIL to be mistaken and mistreated for multiple sclerosis (MS). A much less frequent but existing scenario is the co-occurrence of CADASIL and MS (or MS-like inflammatory condition). Such patients may present with spinal cord lesions, brain or spinal cord enhancing lesions, positive oligoclonal bands and high IgG index in the cerebrospinal fluid and good response to corticosteroids or immunomodulating treatments. CADASIL through various mechanisms may trigger or modulate autoimmune reactions, and either be complicated by an inflammatory component or cause an MS-like disorder.展开更多
Prof.Yang Zhengang’s laboratory at the Institutes of Brain Science,Fudan University,reported subcortical origins of human and monkey neocortical interneurons,which was published in Nature Neuroscience(2013,16(11):158...Prof.Yang Zhengang’s laboratory at the Institutes of Brain Science,Fudan University,reported subcortical origins of human and monkey neocortical interneurons,which was published in Nature Neuroscience(2013,16(11):1588—1597).GABAergic inhibitory interneurons play crucial roles in the development and organization of cortical networks.Nearly all GABAergic neurons in rodent cortex are generated from the ventral telencephalon.展开更多
Carnosine is a dipeptide that scavenges free radicals, inhibits infammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. ...Carnosine is a dipeptide that scavenges free radicals, inhibits infammation 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, Klfiver-Barrera staining, toluidine blue staining and immunofluorescence stain- ing 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
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2015160)
文摘Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.
文摘Objective: Vacuolating megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently described syndrome with autosomal recessive mode of inheritance. Its possible gene was located on chromosomal 22q tel with 3-cM. The purpose of this study was to narrow down the genetical distance on chromosomal 22q tel with MLC. Methods: Thirty-nine MLC patients in 33 families were collected,and the linkage analysis and haplotype analysis of twelve informative families were done, using seven microsatellite markers and four SNP markers. Results: The maximum tow-point LOD score for marker 355c18 was 6.65 at recombination fraction 0.02. The haplotype analysis narrowed down the critical region of MLC to 250 kb on chromosomal 22q tel. Conclusion: One of the causing genes of MLC was located on chromosomal 22q tel with 250 kb. Four candidate genes were considered. The heterogeneity of one informative family indicated possible existence of a second locus for MLC.
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.
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 neural tract responsible for motor function in the human brain. It is mainly related to hand movements （Iang, 2014）. Therefore, recovery of an injured CST contributes to good recovery in stroke patients and a thorough knowledge of the recovery mechanism regarding an injured CST is required for successful brain rehabilitation.
基金supported by the Beijing Municipal Education Commission Science and Technology Development Project, No. KM200910025015
文摘The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities.
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 mo- tor 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 mecha- nism 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 axonal injury （TAI） at subcortical white matter, as detected on fol- low-up diffusion tensor tractography （DTT）.
文摘Here we review a new variety of leukoencephalopathy with infantile megalencephaly and discrepant clinical course (MLC, MIM: 604004). These children had megalencephaly in the first year of life, with or without mild delay of motor function and/or seizures. After a few years, motor handicap was slowly progressive with unsteady gait, serious cerebellar ataxia and mild plasticity. Eventually most of patients were confined to a wheelchair. Meanwhile mental development was relatively preserved, although the learning problems was increased from the midway of elementary school. Most of patients had tonic-clonic seizure and some might advance to status epilepticus. Antiepileptic drugs may effectively control seizure. The disorders of known metabolic defects were excluded. Neurophysiological examination showed that EEG had interictal epileptic discharges on the generalized slow wave background in most patients. The cerebral white matter had diffuse abnormality, with swelling of white matter, and cysts in the frontoparietal and anterior-temporal lobes on MRI examination. Some central white matter structures were spared, such as corpus callosum. The severity of lesions on MRI is inconsistent with the clinical signs. Pathogenesis of this disease was unknown. The pathological findings found a spongiform leukoencephalopathy due to myelin splitting and intramyelinic vacuole formation but without myelin loss. This disease had probably an autosomal recessive inheritance. The gene KIAA027 on 22qtel was responsible for MLC.
文摘Objective: To investigate the association of ischaemic and haemorrhagic strokes with the site of subcortical focal cerebrovascular injuries with affective, behavioural and cognitive dysfunctions in the acute phase and after three months. Sample: 58 patients with focal cerebrovascular injuries;mean age 61.5 ± 13.5, 72.4% male. Control group: 20 healthy subjects, mean age 67.1 ± 7.6, 50% male. Results: Significant differences were observed (p = 0.006) between the acute phase and three months later on the apathy items of the Neuropsychiatric Inventory (NPI) in patients with subcortical stroke. Significant differences were also observed on the affective scale of the BRMS (p = 0.004), the behaviour scale of the Maudsley Obsessive-Compulsive Inventory (MOCI) (p = 0.000), and on the Mini Mental State Examination (MMSE) (p = 0.006). No significant differences were observed on the Hamilton Rating Scale-Depression (HRSM) (p = 0.101). Significant differences were found according to the infarct type: patients with haemorrhagic lesions had higher raw scores on the HRS-D than those with ischaemic lesions (p = 0.024). Conclusions: The performance of patients with subcortical stroke on affective, behavioural and cognitive scales improves after three months. Patients with haemorrhagic lesions are more likely to be depressive than those with ischaemic lesions.
文摘According to the proposed hypothesis, graphic characters trigger the subcortical visual route. The reaction discussed is very weak. Yet, its very existence has an unusual importance: characters and (occluded) venomous snakeskin patterns reveal themselves as conflatable. Furthermore, following tractogra<span><span><span style="font-family:;" "="">- </span></span></span><span><span><span style="font-family:;" "="">phic research, a functional segregation of the subcortical pathway is to be <span>presupposed. Thus, there can’t be a later dissociation of two stimuli pre</span>viously associated. The outc</span></span></span><span><span><span style="font-family:;" "="">omes of lecture will gradually appear probabilistically <span>(much) more peaceful than encountering a venomous snake, though, and</span> thus a continuous lessening of the reaction is expectable. Here, on one hand, it is relevant that the subcortical visual pathway goes to the amygdala. The reactions we describe tap into goal-oriented processes, and they will do that un<span>fettered. On the other hand, in the case of characters, since the beginning,</span> fear has been converted into appetition to a great degree. This process should be fostered in the presence of light. In this way, luminosity might become a conditioned stimulus for attraction. In this case, a Pavlovian addiction for light <span>will foster, yet also—from the point of view of reward fee</span>ling—counterbalance the lessening of the stimulation elicited by characters. The addiction we refer to is one towards light accompanied by graphic signs. Yet, as opposed to the case of the luminous medium, the attention captured by the later ones taken for themselves is continuously reduced.</span></span></span>
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.U20A20191,82071912,12104049,82202291)the Fundamental Research Funds for the Central Universities(Grant No.2021CX11011)the National Key Research and Development Program of China(Grant No.2020YFC2007305).
文摘Objective:We investigated changes in cortico–subcortical spatiotemporal dynamics to explore the treatment mechanisms oftranscranial alternating current stimulation(tACS)in patientswith Parkinson’s disease(PD).Methods:Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 20 patients with PD and 20 normal controls(NC).Each patient with PD received successivemultidisciplinary intensive rehabilitation treatment and tACStreatment over a one-year interval.Individual functional brain network mapping and co-activation pattern(CAP)analysis were performed to characterize cortico–subcortical dynamics.Results:The same tACS electrode placement stimulated different proportions of functional brain networks across the participants.CAP analysis revealed that the visual network,attentional network,and default mode network co-activated with the thalamus,accumbens,and amygdala,respectively.The pattern characterized by thede-activation of the visual network and the activation of the thalamus showed a significantly low amplitude in the patients with PD than inNCs,and this amplitude increased after tACS treatment.Furthermore,the co-occurrence of cortico–subcortical CAPs was significantly higherin patients with PD than in NCs and decreased after tACS treatment.Conclusions:This study investigated cortico–subcortical spatiotemporaldynamics in patients with PD and further revealed the tACS treatmentmechanism.These findings contribute to understanding cortico–subcortical dynamics and exploring noninvasive neuromodulationtargets of cortico–subcortical circuits in brain diseases,such as PD,Alzheimer’s disease,and depression.
基金This work was supported by the National Natural Science Foundation of China(grant number 81671665)Jiangsu Provincial Key Medical Talents(grant number ZDRCA2016085)the Natural Science Foundation of Jiangsu Province(grant number BK20160071).
文摘Vascular cognitive impairment(VCI)describes all forms of cognitive impairment caused by any type of cerebrovascular disease.Early identification of VCI is quite difficult due to the lack of both sensitive and specific biomarkers.Extensive damage to the white matter tracts,which connect the cortical and subcortical regions,has been shown in subcortical VCI(SVCI),the most common subtype of VCI that is caused by small vessel disease.Two specific MRI sequences,including diffusion tensor imaging(DTI)and functional MRI(fMRI),have emerged as useful tools for identifying subtle white matter changes and the intrinsic connectivity between distinct cortical regions.This review describes the advantages of these two modalities in SVCI research and the current DTI and fMRI findings on SVCI.Using DTI technique,a variety of studies found that white matter microstructural damages in the anterior and superior areas are more specific to SVCI.Similarly,functional brain abnormalities detected by fMRI have also been mainly shown in anterior brain areas in SVCI.The characteristic distribution of brain abnormalities in SVCI interrupts the prefrontal-subcortical loop that results in cognitive impairments in particular domains,which further confirms the‘disconnection syndrome’hypothesis.In addition,another MRI technique,arterial spin labelling(ASL),has been used to describe the disconnection patterns in a variety of conditions by measuring cerebral blood flow.The role of the ASL technique in SVCI research is also assessed.Finally,the review proposes the application of multimodality fusion in the investigation of SVCI pathogenesis.
基金supported by grants from the 1·3·5 project for disciplines of excellence,Clinical Research Incubation Project,West China Hospital,Sichuan University(No.2020HXFH012)the National Natural Science Foundation of China(Nos.82071320 and 81870937)。
文摘Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.
基金supported by the Natural Science Foundation of Tianjin Municipal Science and Technology Commission(18JCQNJC10900)Tianjin Natural Science Foundation(17JCZDJC36300)。
文摘Subcortical vascular mild cognitive impairment(svMCI)is a common prodromal stage of vascular dementia.Although mounting evidence has suggested abnormalities in several single brain network metrics,few studies have explored the consistency between functional and structural connectivity networks in svMCI.Here,we constructed such networks using resting-state f MRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls.The functional networks were then parcellated into topological modules,corresponding to several well-defined functional domains.The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level(whole brain and modular level).We found no significant intergroup differences in the functional–structural coupling within the whole brain;however,there was significantly increased functional–structural coupling within the dorsal attention module and decreased functional–structural coupling within the ventral attention module in the svMCI group.In addition,the svMCI patients demonstrated decreased intramodular connectivity strength in the visual,somatomotor,and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network,mainly linking the visual,somatomotor,dorsal attention,ventral attention,and frontoparietal control modules.There was no significant correlation between the altered module-level functional–structural coupling and cognitive performance in patients with svMCI.These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.
基金This study was supported by grants from the National Key Research and Development Program of China （No. 2016YFC1300600）, National Natural Science Foundation of China （No. 81471185）, and National Science and Technology Major Project （No. 2011 ZX09307-001-07）.
文摘Background： Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL） is a hereditar5 small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography （EDI-OCT） to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging （MPRI） findings. Methods： Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First ttospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microblecds were evaluated. All patients and controls underwent EDI-OCT to measure subtbveal choroidal thickness （SFCT）, inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner （AVRin） and outer diameters （AVRout）. The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman＇s correlation was used to investigmc the correlation between retinal vessel changes and MRI lesions. Results： In CADASI L patients, mean SFCT （268.37 ± 46.50 μm） and mean arterial inner diameter （93.46 ± 9.70 gin） were signilicantly lower than that in controls （P 〈 0.00 ）, P = 0.048, respectively）. Mean arterial outer diameter （ 131.74 ± 10.87 μm）, venous inner （ 128.99 ± 13.62 μm） and outer diameter （ 164.82 ±14.77 μm）, and mean arterial （ 19.13 ±1.85 μm） and venous （ 17.91 ±2.76 μm） wall thickness were significantly higher than that in controls （P = 0.023, P 0.004, P 〈 0.001, P 〈 0.001, respectively）. Arterial inner diameter （r= - 0.39, P 0.044）] AVRin （r -0.65, P 〈 0.001）, and AVR,, （r =0.56, P - 0.002） showed a negative correlation with the number of small infarcts. Venous inner diameter （rs=0.46, P= 0.016） showed a positive correlation with the number of small infarcts. Venous inner diameter （r 0.59, P = 0.002）, outer diameter （rs=0.47, P= 0.017）, showed a positive correlation with the number of cerebral microbleeds （CM Bs）. AVRin （r =0.52, P = 0.007） and AVRout （r = -0.40, P =0.048） showed a negative correlation with the number of CMBs. Conclusions： Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might bc a useful evaluation tool for CADASIL patients.
基金the National Key Research and Development Program of China(2018YFA0108503)the National Natural Science Foundation of China(81760251 and 81560234)the Yunnan Provincial Natural Science Foundation(2018FB118 and KKSY201626001).
文摘Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.
基金funded by the National Natural Science Foundation of China(Grant Number:81741053,81501123)the Beijing Natural Science Foundation(Grant Number:7151010,7172217)+5 种基金the Bejing Municipal Science&Technology Commission(Grant Number:Z161100000216133,Z161100004916169)the Beijing Institute for Brain Disorders Foundation(Grant Number:BIBDPXM2014_014226_000016)the Beijing Municipal Natural Science Key Project(Grant Number 15G10050)Bejing key laboratory of molecular diagnosis and study on pediatric genetic discases(Grant Number BZ0317)the National Key Rescarch and Development Program of China(Grant Number:2016YFC1306201,2016YFC0901505)the Fundamental Research Funds for the Central Universities(Grant Number:BMU2017JI002).
文摘Background Megalencephalic leukoencephalopathy with subcortical cysts(MLC)is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inheritance and a different prognosis,characterized by macrocephaly,delayed motor and cognitive development,and bilateral abnormal signals in cerebral white matter(WM)with or without cysts on magnetic resonance imaging(MRI).This study aimed to reveal the clinical and genetic features of MLC patients with GLIALCAM mutations and to explore the brain pathological characteristics and prognosis of mouse models with different modes of inheritance.Methods Clinical information and peripheral venous blood were collected from six families.Genetic analysis was performed by Sanger sequencing of GLIALCAM.Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mouse models were generated based on mutations from patients(c.274C>T(p.Arg92Trp)(c.203A>T(p.Lys68Met),and c.395C>A(p.Thr132Asn))).Brain pathologies of the mouse models at different time points were analyzed.Results Six patients were clinically diagnosed with MLC.Of the six patients,five(Pt1-Pt5)presented with a heterozygous mutation in GLIALCAM(c.274C>T(p.Arg92Trp)or c.275G>C(p.Arg92Pro))and were diagnosed with MLC2B;the remaining patient(Pt6)with two compound heterozygous mutations in GLIALCAM(c.203A>T(p.Lys68Met)and c.395C>A(p.Thr132Asn))was diagnosed with MLC2A.The mutation c.275C>G(p.Arg92Pro)has not been reported before.Clinical manifestations of the patient with MLC2A(Pt6)progressed with regression,whereas the course of the five MLC2B patients remained stable or improved.The Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mouse models showed vacuolization in the anterior commissural WM at 1 month of age and vacuolization in the cerebellar WM at 3 and 6 months,respectively.At 9 months,the vacuolization of the GlialcamiLys68Met/Thr132Asn mouse model was heavier than that of the Glialcam^(Arg92Trp/+)mouse model.Decreased expression of Glialcam in Glialcam^(Arg92Trp/+)and Glialcam^(Lys68Met/Thr132Asn)mice may contribute to the vacuolization.Conclusions Clinical and genetic characterization of patients with MLC and GLIALCAM mutations revealed a novel mutation,expanding the spectrum of GLIALCAM mutations.The first Glialcam mouse model with autosomal recessive inheritance and a new Glialcam mouse model with autosomal dominant inheritance were generated.The two mouse models with different modes of inheritance showed different degrees of brain pathological features,which were consistent with the patients'phenotype and further confirmed the pathogenicity of the corresponding mutations.
文摘Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), is the most common cause of inherited cerebral small vessel disease, inherited stroke and inherited vascular dementia. It is not infrequent for CADASIL to be mistaken and mistreated for multiple sclerosis (MS). A much less frequent but existing scenario is the co-occurrence of CADASIL and MS (or MS-like inflammatory condition). Such patients may present with spinal cord lesions, brain or spinal cord enhancing lesions, positive oligoclonal bands and high IgG index in the cerebrospinal fluid and good response to corticosteroids or immunomodulating treatments. CADASIL through various mechanisms may trigger or modulate autoimmune reactions, and either be complicated by an inflammatory component or cause an MS-like disorder.
基金support by the National Natural Science Foundation of China(Grant Nos.31121061 and 91232723)the Ministry of Science and Technology of China(Grant Nos.2011CB504400 and2010CB945500)
文摘Prof.Yang Zhengang’s laboratory at the Institutes of Brain Science,Fudan University,reported subcortical origins of human and monkey neocortical interneurons,which was published in Nature Neuroscience(2013,16(11):1588—1597).GABAergic inhibitory interneurons play crucial roles in the development and organization of cortical networks.Nearly all GABAergic neurons in rodent cortex are generated from the ventral telencephalon.
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 infammation 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, Klfiver-Barrera staining, toluidine blue staining and immunofluorescence stain- ing 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.
