Prenatal Identification of a Missense Mutation of the L1CAM Gene Associated With Hydrocephalus Using Next-Generation Sequencing.

We present the case of a 35-year-old pregnant woman who visited our department for a routine ultrasonography screening scan for fetus anatomy during the 22nd week of gestation. Our report revealed a male fetus with marked hydrocephalus and severe intrauterine growth retardation. After extensive counseling, the couple decided to proceed with an invasive diagnosis via amniocentesis. The cytogenetic analysis showed findings related to clinical history and ultrasound findings related to the presence of a nucleotide change in c.578T>C with an amino acid change in p.Leu198Pro of the L1CAM gene. The result was reported as a hemizygote missense L1CAM gene variant of unknown significance. After extensive parental counseling, the couple decided on pregnancy termination. We report the present case of L1CAM mutation in p.Leu198Pro to add to the limited knowledge regarding the clinical presentation of mutations of the L1CAM gene with emphasis on prenatal diagnosis.

Intraventricular Pleomorphic Xanthoastrocytoma: A Case Report and Systemic Review.

We present a unique case of a 45-year-old male with cerebral palsy, who experienced walking difficulties and altered consciousness. The initial MRI revealed an intraventricular mass that rapidly enlarged over a month, consisting of two distinct components with different characteristics on CT and MRI, and was associated with agenesis of the corpus callosum. Despite initial treatment, surgical intervention was necessary, where preoperative imaging suggested an exophytically growing glioblastoma. However, postsurgical pathological examination identified the mass as pleomorphic xanthoastrocytoma (PXA), World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) grade 3. This study is notable for its rarity and complexity, challenging standard diagnostic approaches. PXA is an uncommon astrocytic tumor, and its occurrence intraventricularly is extremely rare. This study highlights its unique imaging features and the critical role of MRI in preoperative assessment, underlining the tumor's unusual intraventricular location, and its relationship with corpus callosum agenesis. Our comprehensive review of PXA's history and imaging spectrum offers valuable insights for neuroradiologists and neurosurgeons, emphasizing the diagnostic challenges of such rare tumor locations and the importance of meticulous MRI analysis for accurate diagnosis.

Alterations of interhemispheric functional homotopic connectivity and corpus callosum microstructure in bulimia nervosa.

Background: Accumulating evidence indicates maladaptive neural information interactions between different brain regions underlie bulimia nervosa (BN). However, little is known about the alterations in interhemispheric communication of BN, which is facilitated by the corpus callosum (CC), the major commissural fiber connecting the two hemispheres. To shed light on the interhemispheric communications in BN, the present study aims to explore alterations of interhemispheric homotopic functional connectivity and the CC microstructure in BN. Methods: Based on magnetic resonance imaging (MRI) data collected from 42 BN patients and 38 healthy controls (HCs), the group differences of voxel-mirrored homotopic connectivity (VMHC) index and CC white matter microstructure were compared. Then brain regions with significant group differences in VMHC were selected as seeds for subsequent functional connectivity (FC) analysis. Seed-based fiber tracking and correlation analysis were used to analyze the relationship between VMHC and CC changes. And correlation analysis was used to reveal the correlation between abnormal imaging variables and the clinical features of BN. Results: Compared with HCs, the BN group showed decreased fractional anisotropy (FA) in middle part of CC (CCMid) and increased VMHC in bilateral orbitofrontal cortex (OFC) and middle temporal gyrus (MTG) [false discovery rate (FDR) correction with a corrected threshold of P<0.05]. Subsequent FC analyses indicated increased FC between left OFC and right OFC, bilateral MTG, left middle occipital gyrus and right precuneus (PCUN); between right OFC and left cerebellum crus II and right PCUN; and between left MTG and right inferior temporal gyrus, right cerebellum lobule VI and right medial superior frontal gyrus (FDR correction with a corrected threshold of P<0.05). The VMHC values of OFC and MTG showed no correlations with FA values of the CCMid and the white fibers between the bilateral OFC and MTG were not through the CCMid. In addition, several regions with abnormal FC had a potential correlation trend with abnormal eating behaviors in BN patients (P<0.05, uncorrected). Conclusions: Aberrant interhemispheric homotopic functional connectivity and CC microstructure were observed in BN, and they may be independent of each other. Regions with aberrant interhemispheric homotopic functional connectivity showed hyperconnectivity with regions related to reward processing, body shape perception, and self-reference.

Linked patterns of interhemispheric functional connectivity and microstructural characteristics of the corpus callosum in antipsychotic-naive first-episode schizophrenia.

OBJECTIVE: Many magnetic resonance imaging (MRI) studies have showed significant structural abnormalities of the corpus callosum (CC) and dysregulated interhemispheric functional connectivity (FC) in schizophrenia. Although the hemispheres are mainly linked through CC, few studies directly examined the relationship between aberrant interhemispheric FC and the white matter deficits of the CC in schizophrenia. METHODS: One hundred and sixty-nine antipsychotic-naive first-episode schizophrenia patients (AN-FES) and 214 healthy controls (HCs) were recruited. Diffusional and functional MRI data were obtained for each participant, and fractional anisotropy (FA) values of the five CC subregions and interhemispheric FC for each participant were acquired. Between-group differences in these metrics were compared using multivariate analysis of covariance (MANCOVA). Moreover, sparse canonical correlation analysis (sCCA) was conducted to explore correlations of fibers integrity of the CC subregions with dysregulated interhemispheric FC in patients. RESULTS: Compared with HCs, the patients with schizophrenia showed significantly reduced FA values of the CC subregions and dysregulated connectivity between two cerebral hemispheres. The canonical correlation coefficients identified five significant sCCA modes between FA and FC (r > 0.75, p < 0.001), suggesting strong relationships between FA values of the CC subregions and interhemispheric FC in patients. CONCLUSION: Our findings support a key role of CC in maintaining ongoing functional communication between two cerebral hemispheres, and suggest that microstructural changes of white matter fibers crossing different CC subregions may affect special interhemispheric FC in schizophrenia.

Distribution and Morphological Characteristics of Oligodendrocytes in Selected Areas of the Brain of Male and Female Red Kangaroos (Macropus rufus).

This study was carried out on six adult red kangaroos of both sexes. To determine the location of the oligodendrocytes (OLGs) of the hippocampus (Hip) and corpus callosum (CC), the method of impregnation of the neuroglia with silver salts was applied. The iron distribution in the OLGs was determined by the histochemical method. The Nissl method was used to determine the location of the brain structure and to analyze the number of OLGs. In the Hip, these cells are located one beside another, mainly in blood vessels and neurons; in the neocortex (NC), they are located in layers I-VI; and in the CC, they are arranged in characteristic rows and accompany both nerve fibers and blood vessels. The analysis of the results obtained by the chosen methods in the Hip, NC, and CC in males and females did not show statistically significant differences in the distribution and location of the red kangaroo OLGs. The involvement of these cells is a physiological process that proceeds in a similar manner throughout the life of individuals and actively influences the metabolism of neurons and myelin.

Transmembrane protein 108 inhibits the proliferation and myelination of oligodendrocyte lineage cells in the corpus callosum.

BACKGROUND: Abnormal white matter is a common neurobiological change in bipolar disorder, and dysregulation of myelination in oligodendrocytes (OLs) is the cause. Transmembrane protein 108 (Tmem108), as a susceptible gene of bipolar disorder, is expressed higher in OL lineage cells than any other lineage cells in the central nervous system. Moreover, Tmem108 mutant mice exhibit mania-like behaviors, belonging to one of the signs of bipolar disorder. However, it is unknown whether Tmem108 regulates the myelination of the OLs. RESULTS: Tmem108 expression in the corpus callosum decreased with the development, and OL progenitor cell proliferation and OL myelination were enhanced in the mutant mice. Moreover, the mutant mice exhibited mania-like behavior after acute restraint stress and were susceptible to drug-induced epilepsy. CONCLUSIONS: Tmem108 inhibited OL progenitor cell proliferation and mitigated OL maturation in the corpus callosum, which may also provide a new role of Tmem108 involving bipolar disorder pathogenesis.

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients.

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding. Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD. Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = -1.731 to -0.034). Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.

Abnormal corpus callosum induced by overt hepatic encephalopathy impairs interhemispheric functional coordination in cirrhosis patients.

BACKGROUND: Although overt hepatic encephalopathy (OHE) patients were shown to have bilaterally symmetrical structural and functional abnormalities in the whole brain, few studies have focused on the bilateral cerebral hemisphere commissural fibers and measured functional coordination between bilateral hemispheres. This study aimed to investigate the structural changes of the corpus callosum (CC) and interhemispheric functional coordination in patients with OHE and to test the hypothesis that abnormal CC induced by OHE impairs interhemispheric functional coordination in cirrhosis patients. METHODS: The microstructural integrity and the volumes of each subregion of the CC were analyzed by diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging. Voxel-mirrored homotopic connectivity (VMHC) was derived from resting-state functional magnetic resonance imaging (MRI). RESULTS: Compared with the healthy controls (HCs) and patients without hepatic encephalopathy (noHE), the OHE group showed decreased volumes in all subregions of the CC. In OHE patients, the decreased fractional anisotropy (FA) of CC-5 correlated with decreased VMHC in the middle occipital gyrus (MOG) and precuneus. The value of FA in CC-5 and the volumes of CC-3, CC-4, and CC-5 showed correlations with neuropsychological performance in patients with OHE. CONCLUSIONS: These findings suggest that impairment of interhemispheric white matter pathways may disturb the functional connectivity associated with coordination and neurocognitive performance.

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated.

BACKGROUND: The corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment. METHODS: The study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant. RESULTS: There were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients. CONCLUSIONS: Our findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

Relationship between illness duration, corpus callosum changes, and sustained attention dysfunction in major depressive disorder.

BACKGROUND: Illness duration is the main index of cumulative illness severity during depression progression. Corpus callosum (CC) damage is among the most replicated neurobiological findings in major depressive disorder (MDD). We aimed to investigate the nature and extent of the association between illness duration and CC changes. METHODS: Ninety-six MDD patients and 50 controls underwent diffusion and resting-state functional magnetic resonance imaging (fMRI). White matter micro-structure and inter-hemispheric functional connectivity were quantified by fractional anisotropy (FA) and voxel-mirrored homotopic connectivity (VMHC). The CC was reconstructed by tractography and divided into five sub-regions. The associations of illness duration with FA of each CC sub-region and voxel-wise VMHC were examined using correlation analyses. Also, we investigated the potential relationship between illness duration, CC changes, and clinical variables using mediation analyses. RESULTS: In MDD patients, longer illness duration was selectively associated with lower FA of CC sub-regions 2 [partial correlation coefficient (pr) =-0.269, P=0.009] and 5 (pr=-0.296, P=0.004) as well as higher VMHC in the supplementary motor areas (pr=0.378, P<0.001), precuneus (pr=0.384, P<0.001), and lingual gyrus (pr=0.373, P<0.001) connected by the affected CC sub-regions. Further subgroup analyses demonstrated pronounced FA decrease and VMHC increase in patients with illness duration over 20 years relative to healthy controls (HC) and other patient subgroups with shorter illness durations. Moreover, lower FA of CC sub-regions 2 and 5 mediated the association between longer illness duration and more severe sustained attention dysfunction. CONCLUSIONS: These findings provide evidence for compromised structure yet compensatory function of the CC with increasing depression illness duration, which may inform effective antidepressant treatment strategies at different disease stages.

Morphological alterations of the corpus callosum in antipsychotic-naive first-episode schizophrenia before and 1-year after treatment.

OBJECTIVE: The corpus callosum (CC) is known to be altered in patients with schizophrenia. However, its morphologic characteristics are less well studied in treatment-naive first-episode schizophrenia patients, as is the effect of antipsychotic treatment on this structure. METHODS: T-1 weighted MRI scans were obtained from 160 antipsychotic-naïve first-episode schizophrenia patients (AN-FES) and 155 healthy controls (HCs) before treatment initiation. Among the patients, forty-four were available for follow-up studies after one year of antipsychotic treatment, and were divided into good-outcome (n = 31) and poor-outcome subgroups (n = 13) based on whether there was a 50% reduction in Positive and Negative Symptom Scale (PANSS) total scores from baseline. A computer algorithm was applied to automatically identify the mid-sagittal plane (MSP) and obtain morphological measurement parameters of the CC. RESULTS: Compared with HCs, AN-FES patients showed a significant reduction of thickness in the posterior midbody of the CC. This deficit was correlated with severity of negative symptoms. After one year of antipsychotic treatment, there was no significant change in CC morphological measurements in schizophrenia patients, nor was there a significant difference of CC morphological measurements between good-outcome and poor-outcome subgroups at baseline or at 1-year follow-up. CONCLUSION: Thickness of the posterior midbody of the CC is reduced in the early course of schizophrenia before treatment. This alteration was not affected by antipsychotic treatment and was unrelated to treatment outcome at 1-year.

Anatomical and ultrastructural sex differences in mean diameter and thickness of myelinated axons in adult rat corpus callosum / Diferencias sexuales anatómicas y ultraestructurales del diámetro medio y grosor de los axones mielinizados en el cuerpo calloso de ratas adultas

Sexual dimorphism exists at all levels of the nervous system. These sex differences could underlie genderrelated differences in behavior and neuropsychological function, as well as the gender differences in the prevalence of various mental disorders such as autism, attention deficit disorders, and schizophrenia. Myelination, on the other hand, is a unique cellular process that can have a dramatic impact on the structure and physiology of an axon and its surrounding tissue. The corpus callosum (CC) is the largest of the brain commissures, which connects the cerebral cortices of the two hemispheres, and provides interhemispheric connectivity for information transfer and processing between cortical regions. Variation in the axonal properties of CC will alter the interhemispheric connectivity. The CC consists of myelinated and unmyelinated axons, glial cells and blood vessels. Several functional studies have reported that the function of CC is associated with its axons density and myelination properties. The sexual dimorphism in the axonal content of the CC has always been controversial; hence, the aim of this study was to analyze the differences in axons' diameter and myelin sheath thickness of the CC between male and female rats. For this purpose, five pairs of adult male and female rats were perfused and the CC were removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium of the CC were stained and electron microscopic images were captured using stereological guidelines. Later, the axons diameter and myelin sheath thickness for each subregion were calculated and compared between males and females. Our preliminary findings of the present study indicated region specific differences in the myelinated axon thickness and diameter in the CC between male and female rats.

El dimorfismo sexual existe en todos los niveles del sistema nervioso. Estas diferencias de sexo podrían ser la base de las diferencias de comportamiento y función neuropsicológica relacionadas con el sexo, así como las diferencias en la prevalencia de diversos trastornos mentales, como el autismo, los trastornos por déficit de atención y la esquizofrenia. La mielinización, por otro lado, es un proceso celular único que puede tener un impacto dramático en la estructura y fisiología de un axón y su tejido circundante. El cuerpo calloso (CC) es la mayor comisura cerebral, que conecta las cortezas cerebrales de ambos hemisferios, y proporciona la conectividad interhemisférica para la transferencia y el procesamiento de información entre regiones corticales. La variación en las propiedades axonales de CC alterará la conectividad interhemisférica. El CC consiste en axones mielinizados y no mielinizados, células gliales y vasos sanguíneos. Varios estudios funcionales han informado que la función de CC está asociada con la densidad de axones y las propiedades de mielinización. El dimorfismo sexual en el contenido axonal del CC siempre ha sido controvertido; por lo tanto, el objetivo de este estudio fue analizar las diferencias en el diámetro de los axones y el grosor de la vaina de mielina del CC entre ratas macho y hembra. Para este propósito, se perfundieron cinco pares de ratas macho y hembra adultas y se extrajeron y seccionaron las CC. Se tiñeron cuatro secciones de diferentes subregiones del cuerpo calloso que representan el genu, el cuerpo anterior, el cuerpo posterior y el esplenio y se capturaron imágenes de microscopía electrónicas utilizando referencias estereológicas. Posteriormente se calculó el diámetro de los axones y el grosor de la vaina de mielina para cada subregión y se compararon entre machos y hembras. Nuestros hallazgos preliminares del presente estudio indicaron diferencias específicas en el grosor y diámetro del axón mielinizado en el CC entre ratas macho y hembra.

Aberrant white matter properties of the callosal tracts implicated in girls with attention-deficit/hyperactivity disorder.

Aberrant microstructure of the callosal tracts has been found in boys with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the previously identified white matter (WM) alterations in boys with ADHD are also present in girls with ADHD. Thus, we applied diffusion tensor imaging (DTI) to investigate WM alterations in the callosal tracts in girls with ADHD. In this study, twenty-four adolescent girls (fourteen ADHD patients and ten typically developed girls) were recruited for high-resolution DTI. Automated fiber quantification of the callosum forceps major and the callosum forceps minor was then conducted. Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated to investigate the microstructural integrity of the two callosal tracts. We also investigated correlations between diffusion properties and clinical measurements, including scores on Conners' Parent Rating Scale, the Stroop Color-Word Test, the Wisconsin Card Sorting Test and the Continuous Performance Test, in ADHD patients and typically developed girls. Compared to typically developed adolescent girls, girls with ADHD had reduced FA values at nodes 59-70 and increased RD values at nodes 60-68 along the callosum forceps major. Lower FA values correlated with higher Hyperactivity-Impulsivity scores and lower control quotients, while higher RD values correlated with lower control quotients. This study revealed the disruption of interhemispheric connectivity, particularly across the right side of the occipital CC tract, which might be involved in visual processes in girls with ADHD. These findings enhanced current knowledge about the neuropathological basis of female ADHD.

Gender differences in the rat corpus callosum: An ultrastructure study.

Sexual dimorphism exists at all levels of the nervous system, from genetic, anatomical and system levels. The sexual dimorphism in the axonal content of the corpus callosum (CC) has always been controversial; hence, the aim of this study was to analyse the differences in total, myelinated and unmyelinated axons density of various regions of the CC between male and female rats. To assess that, six pairs of adult male and female rats were perfused and the CC was removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium, were stained, and electron microscopic images were captured using stereological guidelines. Later, the axons density for each subregion was calculated and compared between males and females. The findings of the present study indicated region-specific differences in the myelinated, unmyelinated or the ratio of myelinated/total axons in the CC between male and female rats.

Agenesis and Hypomyelination of Corpus Callosum in Mice Lacking Nsun5, an RNA Methyltransferase.

Williams-Beuren syndrome (WBS) is caused by microdeletions of 28 genes and is characterized by cognitive disorder and hypotrophic corpus callosum (CC). Nsun5 gene, which encodes cytosine-5 RNA methyltransferase, is located in the deletion loci of WBS. We have reported that single-gene knockout of Nsun5 (Nsun5-KO) in mice impairs spatial cognition. Herein, we report that postnatal day (PND) 60 Nsun5-KO mice showed the volumetric reduction of CC with a decline in the number of myelinated axons and loose myelin sheath. Nsun5 was highly expressed in callosal oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) from PND7 to PND28. The numbers of OPCs and OLs in CC of PND7-28 Nsun5-KO mice were significantly reduced compared to wild-type littermates. Immunohistochemistry and Western blot analyses of myelin basic protein (MBP) showed the hypomyelination in the CC of PND28 Nsun5-KO mice. The Nsun5 deletion suppressed the proliferation of OPCs but did not affect transition of radial glial cells into OPCs or cell cycle exit of OPCs. The protein levels, rather than transcriptional levels, of CDK1, CDK2 and Cdc42 in the CC of PND7 and PND14 Nsun5-KO mice were reduced. These findings point to the involvement of Nsun5 deletion in agenesis of CC observed in WBS.

Altered White Matter Organization in the TUBB3 E410K Syndrome.

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T.

The present study examines the change in water diffusion properties of the corpus callosum (CC) and the hippocampus, in response to prolonged hypobaric hypoxia (HH) stress, using in vivo magnetic resonance imaging (MRI) modalities such as T2 relaxometry and diffusion tensor imaging (DTI). Three groups of rats (n=7/group) were exposed to a simulated altitude of 6700m above sea level for the duration of 7, 14 and 21days, respectively. Data were acquired pre-exposure, post-exposure and after 1week of normoxic follow-up in each group. The increment in T2 values with no apparent diffusion coefficient (ADC) change in the CC after 7 and 14days of HH exposure indicated mixed (vasogenic and cytotoxic) edema formation. After 1week of normoxia, 7-day HH-exposed rats showed a decrease in ADC values in the CC, probably due to cytotoxic edema. A delayed decrease in ADC values was observed in the hippocampus after 1week normoxic follow-up in 7- and 14-day HH groups giving an insight of cytotoxic edema formation. Interestingly, 21-day HH-exposed rats did not show change in ADC values. The decrease in T2 values after 14 and 21days in the hippocampal region depicts iron deposition, which was confirmed by histopathology. This study successfully demonstrated the use of MRI modality to trace water diffusion changes in the brain due to prolonged HH exposure.

White matter integrity affected by depressive symptoms in migraine without aura: a tract-based spatial statistics study.

Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self-rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (-) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract-based spatial statistics analyses with multiple diffusion tensor imaging-derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integrity between all patients with MWoA and all healthy controls, between each subgroup (SDS (-) group and SDS (+) group) and healthy controls, and between the SDS (-) and SDS (+) groups. Compared with healthy controls, decreased AD was shown in several WM tracts of the whole MWoA group, SDS (-) group and SDS (+) group. In addition, compared with the SDS (-) group, the SDS (+) group showed decreased FA and increased MD and RD, with conserved AD, including the genu, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculi, the right anterior corona radiata and some other WM tracts, similar to previous findings in depression disorder. Furthermore, mean FA and RD in some of the above-mentioned WM tracts in the SDS (+) group were correlated significantly with SDS scores, including the genu and splenium of the corpus callosum, the right anterior corona radiata and the superior longitudinal fasciculi. Our results suggest that WM integrity may be affected by both depression symptoms (more sensitive as RD) and migraine (more sensitive as AD). The findings may serve as a sensitive biomarker of depression severity in MWoA.

Effect of Ligustrazine on nNOS expression in different encephalic regions after focal cerebral ischemia in adult rats / 西安交通大学学报(医学版)

0.05).In SVZ,nNOS expression in ischemic model group was reduced on days 1-14,but increased on day 21;after Ligustrazine administration,nNOS expression was obviously decreased on days 3-14 in all Ligustrazine dose groups,but began to increase on day 21.In CC,nNOS expression in ischemic model group was reduced on days 3-14,and began to increase on day 21;in the different-dose Ligustrazine groups,nNOS expression was significantly decreased on days 3-14,especially in medium-and high-dose groups,but increased on day 21.In striatum and cortex peri-infarction,nNOS expression in ischemic model group was obviously decreased on days 3 and 7,but enhanced on days 14 and 21;in various-dose Ligustrazine groups,nNOS expression was decreased on days 3-21,especially in medium-and high-dose groups,but increased slightly on day 21.In DG and CA1 areas,nNOS expression in ischemic model group was reduced on days 3 and 7,but began to increase on day 14;nNOS expression in all Ligustrazine groups were decreased during 3-21d.There were significant differences between ischemic model group and different-dose Ligustrazine groups at different time points(P