Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination.

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

5Z-7-Oxozaenol attenuates cuprizone-induced demyelination in mice through microglia polarization regulation.

INTRODUCTION: Demyelination is a key factor in axonal degeneration and neural loss, leading to disability in multiple sclerosis (MS) patients. Transforming growth factor beta activated kinase 1 (TAK1) is a critical molecule involved in immune and inflammatory signaling pathways. Knockout of microglia TAK1 can inhibit autoimmune inflammation of the brain and spinal cord and improve the outcome of MS. However, it is unclear whether inhibiting TAK1 can alleviate demyelination. METHODS: Eight-week-old male c57bl/6j mice were randomly divided into five groups: (a) the control group, (b) the group treated with cuprizone (CPZ) only, (c) the group treated with 5Z-7-Oxozaenol (OZ) only, and (d) the group treated with both cuprizone and 15 µg/30 µg OZ. Demyelination in the mice of this study was induced by administration of CPZ (ig) at a daily dose of 400 mg/kg for consecutive 5 weeks. OZ was intraperitoneally administered at mentioned doses twice a week, starting from week 3 after beginning cuprizone treatment. Histology, rotarod test, grasping test, pole test, Western blot, RT-PCR, and ELISA were used to evaluate corpus callosum demyelination, behavioral impairment, oligodendrocyte differentiation, TAK1 signaling pathway expression, microglia, and related cytokines. RESULTS: Our results demonstrated that OZ protected against myelin loss and behavior impairment caused by CPZ. Additionally, OZ rescued the loss of oligodendrocytes in CPZ-induced mice. OZ inhibited the activation of JNK, p65, and p38 pathways, transformed M1 polarized microglia into M2 phenotype, and increased brain-derived neurotrophic factor (BDNF) expression to attenuate demyelination in CPZ-treated mice. Furthermore, OZ reduced the expression of proinflammatory cytokines and increases anti-inflammatory cytokines in CPZ-treated mice. CONCLUSION: These findings suggest that inhibiting TAK1 may be an effective approach for treating demyelinating diseases.

Structural Alterations of the Corpus Callosum in Children With Infantile Hydrocephalus.

This study investigates structural alterations of the corpus callosum in children diagnosed with infantile hydrocephalus. We aim to assess both macrostructural (volume) and microstructural (diffusion tensor imaging metrics) facets of the corpus callosum, providing insights into the nature and extent of alterations associated with this condition. Eighteen patients with infantile hydrocephalus (mean age = 9 years) and 18 age- and sex-matched typically developing healthy children participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were used to assess corpus callosum volume and microstructure, respectively. Our findings reveal significant alterations in corpus callosum volume, particularly in the posterior area, as well as distinct microstructural disparities, notably pronounced in these same segments. These results highlight the intricate interplay between macrostructural and microstructural aspects in understanding the impact of infantile hydrocephalus. Examining these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on corpus callosum integrity, given its pivotal role in interhemispheric communication. This knowledge offers a more nuanced perspective on neurologic disorders and underscores the significance of investigating the corpus callosum's health in such contexts.

MR insights into fetal brain development: what is normal and what is not.

Fetal brain development is a complex, rapid, and multi-dimensional process that can be documented with MRI. In the second and third trimesters, there are predictable developmental changes that must be recognized and differentiated from disease. This review delves into the key biological processes that drive fetal brain development, highlights normal developmental anatomy, and provides a framework to identify pathology. We will summarize the development of the cerebral hemispheres, sulci and gyri, extra-axial and ventricular cerebrospinal fluid, and corpus callosum and illustrate the most common abnormal findings in the clinical setting.

Retrospective analysis of the prognostic factors of fetal corpus callosum dysplasia.

BACKGROUND: To analyze the genetic characteristics and long-term outcomes of fetuses with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC). METHODS: A total of 42 fetuses with DCC (n = 36) or PACC (n = 6) were retrospectively analyzed from January 2016 to December 2022 at the Peking University First Hospital. The cohort was categorized into isolated (15/42, 36%) and nonisolated groups (27/42, 64%), and differences in the genetic abnormalities and long-term outcomes between the two groups were analyzed. DCC was subdivided into short CC, thin CC, and thick CC. The outcomes of the three different types of DCC were analyzed and discussed. RESULTS: (1) Thirty-nine of the 42 cases underwent CMA (chromosomal microarray analysis) and CMA + WES (whole exome sequencing), with 13/15 cases in isolated group and 26/27 cases in nonisolated group. Only pathogenic or likely pathogenic (P/LP) variants were considered, identifying P/LP variants in 2/13 cases in isolated group and 12/26 cases in nonisolated group. There was no significant difference between the two groups (χ² = 3.566, P = 0.05897). (2) In the isolated group, 8 cases were terminated, and 7 cases were delivered. Postnatal follow-up detected 1 case of gross motor development delay one year after birth; no obvious abnormalities were found in the other six cases. In the nonisolated group, 21 cases were terminated, and 6 cases were delivered. Postnatal follow-up detected 4 cases of children with different degrees of language, motor and intelligence abnormalities; 1 case died 10 days after birth. No obvious abnormalities were observed in one case. Six cases (86%, 6/7) in the isolated group showed normal development, compared with 1 case (17%, 1/6) in the nonisolated group, with a significant difference (χ² = 6.198, P = 0.01279). (3) In DCC, the delivery rates of short CCs (18 cases), thin CCs (13 cases), and thick CCs (5 cases) were 17% (3/18), 54% (7/13), and 20% (1/5), respectively, with good outcomes observed in 0% (0/3), 71% (5/7), and 0% (0/1), respectively. P/LP variants were found in 6/17 cases of short CC, 3/12 cases of thin CC, and 2/5 cases of thick CC. CONCLUSIONS: Fetuses with DCC or PACC combined with other structural abnormalities had a poor long-term prognosis compared with the isolated group. Patients with thin CCs had a higher probability of a good prognosis than those with short or thick CCs.

Cortical mapping of callosal connections in healthy young adults.

The corpus callosum (CC) is the principal white matter bundle supporting communication between the two brain hemispheres. Despite its importance, a comprehensive mapping of callosal connections is still lacking. Here, we constructed the first bidirectional population-based callosal connectional atlas between the midsagittal section of the CC and the cerebral cortex of the human brain by means of diffusion-weighted imaging tractography. The estimated connectional topographic maps within this atlas have the most fine-grained spatial resolution, demonstrate histological validity, and were reproducible in two independent samples. This new resource, a complete and comprehensive atlas, will facilitate the investigation of interhemispheric communication and come with a user-friendly companion online tool (CCmapping) for easy access and visualization of the atlas.

Early-stage volume losses in the corpus callosum and thalamus predict the progression of brain atrophy in patients with multiple sclerosis.

BACKGROUND: A method that can be used in the early stage of multiple sclerosis (MS) to predict the progression of brain volume loss (BVL) has not been fully established. METHODS: To develop a method of predicting progressive BVL in patients with MS (pwMS), eighty-two consecutive Japanese pwMS-with either relapsing-remitting MS (86%) or secondary progressive MS (14%)-and 41 healthy controls were included in this longitudinal retrospective analysis over an observational period of approximately 3.5 years. Using a hierarchical cluster analysis with multivariate imaging data obtained by FreeSurfer analysis, we classified the pwMS into clusters. RESULTS: At baseline and follow-up, pwMS were cross-sectionally classified into three major clusters (Clusters 1, 2, and 3) in ascending order by disability and BVL. Among the patients included in Cluster 1 at baseline, approximately one-third of patients (12/52) transitioned into Cluster 2 at follow-up. The volumes of the corpus callosum, the thalamus, and the whole brain excluding the ventricles were significantly decreased in the transition group compared with the nontransition group and were found to be the most important predictors of transition. CONCLUSION: Decreased volumes of the corpus callosum and thalamus in the relatively early stage of MS may predict the development of BVL.

Applying the en-bloc technique in corpus callosum glioblastoma surgery contributes to maximal resection and better prognosis: a retrospective study.

BACKGROUND: Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. METHODS: A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. RESULTS: Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P < 0.001; r = 0.720, P < 0.001 for PSM analysis), indicating that applying the en-bloc technique could contribute to enlarged maximal resection. Further survival analysis confirmed that applying the en-bloc technique and achieving supramaximal resection could significantly prolong OS and PFS, and multivariate analysis suggested that tumor location, pathology, EOR and the en-bloc technique could be regarded as independent prognostic indicators for OS in patients with ccGBMs, and pathology, EOR and the en-bloc technique were independently correlated with patient's PFS. Interestingly, the en-bloc technique also provided a marked reduction in the risk of tumor recurrence compared with the no-en-bloc technique in tumors undergoing TR, indicating that the essential role of the en-bloc technique in ccGBM surgery (HR: 0.712; 95% CI: 0.535-0.947; P = 0.02). CONCLUSIONS: The en-bloc technique could contribute to achieving an enlarged maximal resection and could significantly prolong overall survival and progression-free survival in patients with ccGBMs.

A case of Wilson's disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature.

BACKGROUND: Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. CASE PRESENTATION: The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson's disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson's disease combined with intracranial lipoma and corpus callosum dysplasia. The patient's WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient's abnormal copper metabolism may promote the growth of intracranial lipoma. CONCLUSION: The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases' more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

Transcriptomic Profiling Reveals Neuroinflammation in the Corpus Callosum of a Transgenic Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive cognitive decline, affecting a significant portion of the aging population. While the cerebral cortex and hippocampus have been the primary focus of AD research, accumulating evidence suggests that white matter lesions in the brain, particularly in the corpus callosum, play an important role in the pathogenesis of the disease. OBJECTIVE: This study aims to investigate the gene expression changes in the corpus callosum of 5xFAD transgenic mice, a widely used AD mouse model. METHODS: We conducted behavioral tests for spatial learning and memory in 5xFAD transgenic mice and performed RNA sequencing analyses on the corpus callosum to examine transcriptomic changes. RESULTS: Our results show cognitive decline and demyelination in the corpus callosum of 5xFAD transgenic mice. Transcriptomic analysis reveals a predominance of upregulated genes in AD mice, particularly those associated with immune cells, including microglia. Conversely, downregulation of genes related to chaperone function and clock genes such as Per1, Per2, and Cry1 is also observed. CONCLUSIONS: This study suggests that activation of neuroinflammation, disruption of chaperone function, and circadian dysfunction are involved in the pathogenesis of white matter lesions in AD. The findings provide insights into potential therapeutic targets and highlight the importance of addressing white matter pathology and circadian dysfunction in AD treatment strategies.

Outcome of partial agenesis of corpus callosum.

BACKGROUND: The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade because of improved imaging techniques, scanning skills, and the routine implementation of transvaginal neurosonography. OBJECTIVE: Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies, and the perinatal outcomes. STUDY DESIGN: We performed a retrospective analysis of cases from January 2007 to December 2017 with corpus callosum anomalies, either referred for a second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from the analysis. Standardized investigation included a detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array comparative genomic hybridization) and fetal magnetic resonance imaging. The pregnancy outcome was collected, and pathologic investigation in case of termination of the pregnancy or fetal or neonatal loss was compared with the prenatal findings. The pregnancy and fetal or neonatal outcomes were reported. The neurologic assessment was conducted by a pediatric neurologist using the Bayley Scales of Infant Development-II and the standardized Child Development Inventory when the Bayley investigation was unavailable. RESULTS: Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded because of complete agenesis, and 86 fetuses had partial agenesis (58.1%). In 20 cases, partial agenesis (23.2%) was isolated, whereas 66 (76.7%) presented with different malformations among which 29 cases (43.9%) were only central nervous system lesions, 21 cases (31.8%) were non-central nervous system lesions, and 16 cases (24.3%) had a combination of central nervous system and non-central nervous system lesions. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable (24.29 [standard deviation, 5.05] weeks and 24.71 [standard deviation, 5.35] weeks, respectively). Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of the pregnancy. Neurologic follow-up data were available for 35 children. The overall neurologic outcome was normal in 21 of 35 children (60%); 3 of 35 (8.6%) showed mild impairment and 6 of 35 (17.1%) showed moderate impairment. The remaining 5 of 35 (14.3%) had severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range, 36-52 months) and 73.3 months (range, 2-138 months) for the nonisolated form. CONCLUSION: Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal magnetic resonance imaging to describe its morphology and the associated anomalies. Genetic anomalies are frequently present in nonisolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and to confirm its isolated nature to enhance parental counseling. Although 60% of children with prenatal diagnosis of isolated agenesis have a favorable prognosis later in life, they often have mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

Investigation into white matter microstructure differences in visual training by using an automated fiber tract subclassification segmentation quantification method.

Visual training has emerged as a useful framework for investigating training-related brain plasticity, a highly complex task involving the interaction of visual orientation, attention, reasoning, and cognitive functions. However, the effects of long-term visual training on microstructural changes within white matter (WM) is poorly understood. Therefore, a set of visual training programs was designed, and automated fiber tract subclassification segmentation quantification based on diffusion magnetic resonance imaging was performed to obtain the anatomical changes in the brains of visual trainees. First, 40 healthy matched participants were randomly assigned to the training group or the control group. The training group underwent 10 consecutive weeks of visual training. Then, the fiber tracts of the subjects were automatically identified and further classified into fiber clusters to determine the differences between the two groups on a detailed scale. Next, each fiber cluster was divided into segments that can analyze specific areas of a fiber cluster. Lastly, the diffusion metrics of the two groups were comparatively analyzed to delineate the effects of visual training on WM microstructure. Our results showed that there were significant differences in the fiber clusters of the cingulate bundle, thalamus frontal, uncinate fasciculus, and corpus callosum between the training group compared and the control group. In addition, the training group exhibited lower mean fractional anisotropy, higher mean diffusivity and radial diffusivity than the control group. Therefore, the long-term cognitive activities, such as visual training, may systematically influence the WM properties of cognition, attention, memory, and processing speed.

Iatrogenic Shapiro syndrome: a case report.

OBJECTIVES: Shapiro's syndrome (SS) is a rare condition characterized by spontaneous periodic hypothermia. The underlying pathophysiological mechanisms and etiology of this syndrome remain controversial, and fewer than 100 cases have been reported to date. The objective of this case report is to present a unique iatrogenic case of SS and contribute additional insights into the underlying etiology of this rare disorder. METHODS: We conducted an analysis of existing medical literature and described a clinical case of SS secondary to a neurosurgical procedure. RESULTS: To our knowledge, we present the first iatrogenic case of SS in a 53-year-old woman who underwent a partial right parieto-occipital lobectomy in 2003 as a treatment for refractory epilepsy. Several years after the surgical procedure, she began experiencing recurrent episodes of hypothermia. Brain magnetic resonance imaging (MRI) revealed the absence of the splenium of the corpus callosum (CC) and pituitary hyperplasia. After ruling out other potential causes of hypothermia, a diagnosis of SS was made. DISCUSSION: The most plausible mechanism to explain the recurrent hypothermia associated with SS in our patient is a probable disruption of the pathways involved in thermoregulation through the CC as a consequence of the surgical procedure. This case report provides further insights into the etiology of this rare disorder.

Coexisting bilateral ciliochoroidal effusion syndrome and an isolated cytotoxic corpus callosum lesion in dengue fever.

Dengue fever is a major health concern in India. There are various reports in the literature regarding the ocular manifestations of this febrile illness. We are reporting a rare case of a woman in her late 30s who developed coexisting bilateral ciliochoroidal effusion syndrome with an isolated cytotoxic corpus callosum lesion associated with dengue febrile illness. To the best of our knowledge, this is the first case of its kind. It opens the avenues for neurological and radioimaging attention for such cases with bilateral ciliochoroidal effusion syndrome.

Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

The neuroprotective potential of mesenchymal stem cells from bone marrow and human exfoliated deciduous teeth in a murine model of demyelination.

INTRODUCTION: Multiple sclerosis (MS) is characterized by chronic inflammation, demyelination, and axonal degeneration within the central nervous system (CNS), for which there is no current treatment available with the ability to promote neuroprotection or remyelination. Some aspects of the progressive form of MS are displayed in the murine cuprizone model, where demyelination is induced by the innate immune system without major involvement of the adaptive immune system. Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory and neuroprotective potential. In this study, we aimed to assess the neuroprotective potential of MSCs from bone marrow (BM-MSCs) and stem cells from human exfoliated deciduous teeth (SHED) in the cuprizone model. METHODS: Human BM-MSCs and SHED were isolated and characterized. Nine-week-old female C57BL/6 mice were randomized to receive either human BM-MSCs, human SHED or saline intraperitoneally. Treatments were administered on day -1, 14 and 21. Outcomes included levels of local demyelination and inflammation, and were assessed with immunohistochemistry and histology. RESULTS: BM-MSCs were associated with increased myelin content and reduced microglial activation whereas mice treated with SHED showed reduced microglial and astroglial activation. There were no differences between treatment groups in numbers of mature oligodendrocytes or axonal injury. MSCs were identified in the demyelinated corpus callosum in 40% of the cuprizone mice in both the BM-MSC and SHED group. CONCLUSION: Our results suggest a neuroprotective effect of MSCs in a toxic MS model, with demyelination mediated by the innate immune system.