Corpus Callosum Research Articles

White Matter Microstructure Organization Across the Transition to Fatherhood

The transition to parenthood remains an understudied window of potential neuroplasticity in the adult brain. White matter microstructural (WMM) organization, which reflects structural connectivity in the brain, has shown plasticity across the lifespan. No studies have examined how WMM organization changes from the prenatal to postpartum period in men becoming fathers. This study investigates WMM organization in men transitioning to first-time fatherhood. We performed diffusion-weighted imaging to identify differences in WMM organization, as indexed by fractional anisotropy (FA). We also investigated whether FA changes were associated with fathers’ postpartum mental health. Associations between mental health and WMM organization have not been rarely examined in parents, who may be vulnerable to mental health problems. Fathers exhibited reduced FA at the whole-brain level, especially in the cingulum, a tract associated with emotional regulation. Fathers also displayed reduced FA in the corpus callosum, especially in the forceps minor, which is implicated in cognitive functioning. Postpartum depressive symptoms were linked with increases and decreases in FA, but FA was not correlated with perceived or parenting stress. Findings provide novel insight into fathers’ WMM organization during the transition to parenthood and suggest postpartum depression may be linked with fathers’ neuroplasticity during the transition to parenthood.

Non-local diffusion-based biomarkers in patients with cocaine use disorder

Cocaine use disorder (CUD) is widely known to result in neurological reconfiguration which can be observed via local diffusivity characteristics of the brain. These changes can be highly correlated while simultaneously variable across patients with different comorbidities or histories of substance use. This implies that more complex neuroimage analysis tools may be necessary to better detect specific biomarkers that vary across these dimensions. We investigated white and gray matter integrity using voxel-based diktiometry (VBD) on whole brain diffusion tensor images (DTI) across a database of CUD patients and healthy controls using a purely data-driven approach. These VBD maps reveal significant cortical and subcortical differences that are indicative of these neural modifications including the insula, cerebellum, ventricles, thalamo-cortical radiations, and corpus callosum bundles. In order to disambiguate these results and investigate the heterogeneity of CUD, the VBD maps have been decomposed into five decorrelated biomarkers: one in the region surrounding the left insula, one implicating the corpus callosum, two concentrated in the left cerebellum, and the last concerning a proximal region of the interhemispheric fissure which serve as potential biomarkers playing a role in CUD. These decorrelated biomarkers have themselves been correlated with consumption patterns and psychiatric and borderline personality disorder scores on the CUD patient group. This preliminary approach to using machine learning techniques to both detect and disambiguate complex non-linear patterns shows promise for better understanding complex and heterogeneous disorders such as CUD.

Is autism a PIN1 deficiency syndrome? A proposed etiological role for glyphosate.

Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.

Prenatal ultrasound reassessment of the corpus callosum based on cortical connectivity information

IntroductionRoutine prenatal ultrasound assessment of the corpus callosum (CC) does not reflect information on fibrous connections. The primary purpose was to construct detailed reference ranges of quantitative characteristics of the foetal CC based on cortical connectivity information. Secondary goals were to examine for sex differences and assess the validity of the measurement technique for cases with CC dysplasia.Material and methodsPregnant women referred to a tertiary centre for sonographic examination were recruited to undergo a detailed foetal scan from 19 to 40 weeks. The foetal CC was divided into 5 distinct segments using the Hofer & Frahm classification technique. The thickness of each segment and the overall length of the CC were measured. Additionally, a segmental evaluation was conducted on partial agenesis of the CC. The inter- and intraobserver variability were assessed by interclass correlation coefficients. Regression analysis was used to determine the association between the biological measurements and gestational age.ResultsA total of 852 foetuses (403 males and 449 females) were included in the final analysis. Intra- and interobserver reliability coefficients ranged from 0.86 to 0.98 and 0.84 to 0.97, respectively. Reference ranges were established for the thickness and length of its segments. We observed that the biometric measurements of the foetal CC showed a curvilinear increase with gestational age. There was a statistically significant sex effect for the CC. At the average gestation age 29.6 weeks, the genu, anterior midbody, posterior midbody, and isthmus of male foetuses were 0.06280 mm, 0.04435 mm, 0.01731 mm, and 0.01556 mm, respectively, thicker than those of female foetuses, whereas the splenium of the female foetus was 0.06583 mm thicker than the male foetus.ConclusionsThe study uncovers distinct patterns of thickness and length growth in the foetal CC and establishes precise reference ranges. These findings can aid in evaluating normal brain development and conducting comprehensive assessments of CC abnormalities.

Acetyl-L-carnitine Improves Depressive-like Behaviors Through Nitric Oxide Modulation in the Cuprizone Intoxication Mouse Model of Multiple Sclerosis

Background: Demyelination and inflammation are the most common pathobiological manifestations contributing to depression in multiple sclerosis (MS). Objectives: The current study aimed to evaluate the effects of acetyl-L-carnitine (ALC) in attenuating depressive-like symptoms in the cuprizone intoxication mouse model. Methods: C57BL/6 mice were categorized into three groups (n = 6 each) as follows: The control animals (CTL), the cuprizone-intoxicated mice (CPZ), and the group that received cuprizone and acetyl-L-carnitine (CPZ+ALC). Depressive-like behaviors were evaluated by the forced swim test (FST) and the tail suspension test (TST). The prefrontal cortex (PFC) and corpus callosum (CC) areas were assessed in terms of histopathology, biochemistry, and gene expression. Results: Following oral gavage of ALC, the immobility time, which represents the despairing time, significantly decreased compared to the CPZ group. Histopathological evaluation showed that remyelination in the CC increased significantly in animals receiving ALC compared to the CPZ mice. Acetyl-L-carnitine considerably decreased the nitric oxide (NO) level in the PFC of the brain in the demyelinated mice compared to the CPZ group. The qRT-PCR results revealed that ALC significantly increased neuronal nitric oxide synthase (nNOS) expression but decreased inducible nitric oxide synthase (iNOS) gene expression compared to the CPZ group. Conclusions: ALC attenuated depressive-like behaviors in the cuprizone demyelination mouse model of MS. These neuroprotective effects of ALC may be exerted by facilitating the remyelination process and modulating the NO level in the PFC.

Long-term demyelination and aging-associated changes in mice corpus callosum; evidence for the role of accelerated aging in remyelination failure in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder affecting the central nervous system. Evidence suggests that age-related neurodegeneration contributes to disability progression during the chronic stages of MS. Aging is characterized by decreased regeneration potential and impaired myelin repair in the brain. It is hypothesized that accelerated cellular aging contributes to the functional decline associated with neurodegenerative diseases. We assessed the impact of aging on myelin content in the corpus callosum (CC) and compared aging with the long-term demyelination (LTD) consequents induced by 12 weeks of feeding with a cuprizone (CPZ) diet. Initially, evaluating myelin content in 2-, 6-, and 18-month-old mice revealed a reduction in myelin content, particularly at 18 months. Myelin thickness was decreased and the g-ratio increased in aged mice. Although a lower myelin content and higher g-ratio were observed in LTD model mice, compared to the normally aged mice, both aging and LTD exhibited relatively similar myelin ultrastructure. Our findings provide evidence that LTD exhibits the hallmarks of aging such as elevated expression of senescence-associated genes, mitochondrial dysfunction, and high level of oxidative stress as observed following normal aging. We also investigated the senescence-associated β-galactosidase activity in O4+ late oligodendrocyte progenitor cells (OPCs). The senescent O4+/β-galactosidase+ cells were elevated in the CPZ diet. Our data showed that the myelin degeneration in CC occurs throughout the lifespan, and LTD induced by CPZ accelerates the aging process which may explain the impairment of myelin repair in patients with progressive MS.

P.105 Corpus callosum changes in children affected by infantile hydrocephalus

Background: Infantile hydrocephalus is characterized by an atypical accumulation of cerebrospinal fluid in the brain, diagnosed and treated before the age of 2 years. Hydrocephalus development is linked to thinning of the corpus callosum (CC), mainly due to the expansion of lateral ventricles, causing upward elevation and compression of periventricular and subcortical white matter. Methods: This study investigates structural alterations in the CC in children diagnosed with infantile hydrocephalus. We examined both macrostructural and microstructural facets of the CC, providing insights into the nature and extent of alterations associated with this condition. 18 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 utilized to assess CC volume and microstructure, respectively. Results: Our findings reveal reductions in CC volume, particularly in posterior area, and distinct microstructural disparities, notably pronounced in these same segments. Conclusions: Investigating these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on CC integrity, given its role as a neural bridge. This knowledge offers a more nuanced perspective on neurological disorders and underscores the significance of investigating the CC’s health in such contexts.

Proteomic dissection of vanishing white matter pathogenesis

Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear which factors contribute to VWM pathogenesis. Here, we investigated the basis of VWM pathogenesis using the 2b5ho mouse model. We first mapped the temporal proteome in the cerebellum, corpus callosum, cortex, and brainstem of 2b5ho and wild-type (WT) mice. Protein changes observed in 2b5ho mice were then cross-referenced with published proteomic datasets from VWM patient brain tissue to define alterations relevant to the human disease. By comparing 2b5ho mice with their region- and age-matched WT counterparts, we showed that the proteome in the cerebellum and cortex of 2b5ho mice was already dysregulated prior to pathology development, whereas proteome changes in the corpus callosum only occurred after pathology onset. Remarkably, protein changes in the brainstem were transient, indicating that a compensatory mechanism might occur in this region. Importantly, 2b5ho mouse brain proteome changes reflect features well-known in VWM. Comparison of the 2b5ho mouse and VWM patient brain proteomes revealed shared changes. These could represent changes that contribute to the disease or even drive its progression in patients. Taken together, we show that the 2b5ho mouse brain proteome is affected in a region- and time-dependent manner. We found that the 2b5ho mouse model partly replicates the human disease at the protein level, providing a resource to study aspects of VWM pathogenesis by highlighting alterations from early to late disease stages, and those that possibly drive disease progression.

E.2 Proof of concept for liquid biopsy: positive correlation between extracellular vesicles shed by high grade gliomas and volume of hypervascular tumour tissue on MRI

Background: High grade gliomas (HGGs) shed extracellular vesicles (EVs) into the bloodstream. EV-derived RNA (EV-RNA) can be detected in plasma, making it a potential biomarker for HGG recurrence after treatment. We sought to establish a baseline relationship between EV-RNA in plasma and hypervascular HGG tissue on MRI. Methods: Eight patients with a new diagnosis of HGG had measurements of plasma EV-RNA and contemporaneous dynamic susceptibility contrast (DSC) MRI. Patient-specific median signal intensity of corpus callosum (mSI-CC) was determined from 10 measurements on the relative cerebral blood volume (rCBV) map. Tumour tissue with signal intensity > mSI-CC and > 2x, > 3x, > 4x and > 5x mSI-CC was segmented on the rCBV map. EV-RNA plasma concentration was correlated with tissue volumes. Results: Pearson correlation showed a significant positive relationship between EV-RNA plasma concentration and tissue volume with signal intensity > mSI-CC (r(6) = 0.899, p = 0.002). No significant relationship could be detected for progressively smaller tissue volumes with signal intensity > 2x, > 3x, > 4x and > 5x mSI-CC. Conclusions: EV-RNA plasma concentration correlates strongly with the total volume of hypervascular HGG tissue on DSC MRI at baseline and merits further evaluation as a biomarker of tumour behaviour in longitudinal imaging studies.

Genetic etiology of agenesis of the corpus callosum: a retrospective single-center cohort analysis of 114 fetuses.

The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined.

Pathologic TDP-43 downregulates myelin gene expression in the monkey brain.

Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states,physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured usingan immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

Low-Temperature Plasma Pretreatment Enhanced Cholesterol Detection in Brain by Desorption Electrospray Ionization-Mass Spectrometry Imaging.

Cholesterol is a primary lipid molecule in the brain that contains one-fourth of the total body cholesterol. Abnormal cholesterol homeostasis is associated with neurodegenerative disorders. Mass spectrometry imaging (MSI) technique is a powerful tool for studying lipidomics and metabolomics. Among the MSI techniques, desorption electrospray ionization-MSI (DESI-MSI) has been used advantageously to study brain lipidomics due to its soft and ambient ionization nature. However, brain cholesterol is poorly ionized. To this end, we have developed a new method for detecting brain cholesterol by DESI-MSI using low-temperature plasma (LTP) pretreatment as an ionization enhancement. In this method, the brain sections were treated with LTP for 1 and 2 min prior to DESI-MSI analyses. Interestingly, the MS signal intensity of cholesterol (at m/z 369.35 [M + H - H2O]+) was more than 2-fold higher in the 1 min LTP-treated brain section compared to the untreated section. In addition, we detected cholesterol, more specifically excluding isomers by targeted-DESI-MSI in multiple reaction monitoring (MRM) mode and similar results were observed: the signal intensity of each cholesterol transition (m/z 369.4 → 95.1, 109.1, 135.1, 147.1, and 161.1) was increased by more than 2-fold due to 1 min LTP treatment. Cholesterol showed characteristic distributions in the fiber tract region, including the corpus callosum and anterior commissure, anterior part of the brain where LTP markedly (p < 0.001) enhanced the cholesterol intensity. In addition, the distributions of some unknown analytes were exclusively detected in the LTP-treated section. Our study revealed LTP pretreatment as a potential strategy to ionize molecules that show poor ionization efficiency in the MSI technique.

Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia.

Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). Brain MRI studies of eighty-three term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) 4 to 6th days were retrospectively re-evaluated by two radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (p = 0.02 and p = 0.03; respectively) and ADCmin (p = 0.03 and p = 0.04; respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (p = 0.04) and normal development (p = 0.04) via cytotoxic edema of the thalamus, corpus striatum and diffuse cerebral cortical. The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimate similarly with volumetric ADC-HA and the conventional assessment of the ADC map. This study compare early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We couldn't find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.

Facial emotion recognition function and white matter microstructural alterations in drug-naive, comorbidity-free autism.

Individuals with autism spectrum disorder have deficits in facial emotion recognition and white matter microstructural alterations. Nonetheless, most previous studies were confounded by different variables, such as psychiatric comorbidities and psychotropic medications used by ASD participants. Also, it remains unclear how exactly FER deficits are related to white matter microstructural alterations in ASD. Accordingly, we aimed to investigate the FER functions, white matter microstructure, and their relationship in drug-naive and comorbidity-free ASD individuals. 59 ASD individuals and 59 typically developed individuals were included, where 46 ASD and 50 TD individuals completed FER tasks. Covariance analysis showed scores were lower in both basic and complex FER tasks in the ASD group. Tract-Based Spatial Statistics showed FA values in widespread white matter fibers were lower in the ASD group than in the TD group, including forceps major and forceps minor of the corpus callosum, anterior thalamic radiation, corticospinal tract, cingulum, inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus. Moreover, in the TD group but not the ASD group, the performance in the complex FER task was negatively correlated with the FA value in some white matter fibers, including forceps major of the corpus callosum, ATR, CT, cingulum, IFOF, ILF, SLF. Our study suggests children with ASD may experience deficits in facial emotion recognition and exhibit alterations in white matter microstructure. More importantly, our study indicates that white matter microstructural alterations may be involved in FER deficits in children with ASD.

Evolution of brain injury and neurological dysfunction after cardiac arrest in the rat - A multimodal and comprehensive model.

Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.

Corpus Callosum Lymphoma in an Immunocompetent Patient: A Case Report

Primary central nervous system lymphoma (PCNSL) involving the corpus callosum is rare and diagnostically challenging. We report a 63-year-old female with cognitive impairment, and personality changes. MRI showed a hyperintense lesion in the corpus callosum, and biopsy confirmed diffuse large B-cell lymphoma (DLBCL). This case highlights the importance of considering PCNSL in differential diagnoses of corpus callosum lesions and underscores the necessity for prompt, aggressive treatment despite a guarded prognosis.

Volumetric and diffusion MRI abnormalities associated with dysarthria in multiple sclerosis

Abstract Up to half of all people with multiple sclerosis experience communication difficulties due to dysarthria, a disorder that impacts the motor aspects of speech production. Dysarthria in multiple sclerosis is linked to cerebellar dysfunction, disease severity and lesion load, but the neuroanatomical substrates of these symptoms remain unclear. In this study, 52 participants with multiple sclerosis and 14 age- and sex-matched healthy controls underwent structural and diffusion MRI, clinical assessment of disease severity and cerebellar dysfunction, and a battery of motor speech tasks. Assessments of regional brain volume and white matter integrity, and their relationships with clinical and speech measures, were undertaken. White matter tracts of interest included the interhemispheric sensorimotor tract, cerebello-thalamo-cortical tract, and arcuate fasciculus, based on their roles in motor and speech behaviours. Volumetric analyses were targeted to Broca’s area, Wernicke’s area, the corpus callosum, thalamus, and cerebellum. Our results indicated that multiple sclerosis participants scored worse on all motor speech tasks. Fixel-based diffusion MRI analyses showed significant evidence of white matter tract atrophy in each tract of interest. Correlational analyses further indicated that higher speech naturalness - a perceptual measure of dysarthria – and lower reading rate were associated with axonal damage in the interhemispheric sensorimotor tract and left arcuate fasciculus in people with multiple sclerosis. Axonal damage in all tracts of interest also correlated with clinical scales sensitive to cerebellar dysfunction. Participants with multiple sclerosis had lower volumes of the thalamus and corpus callosum compared to controls, though no brain volumetrics correlated with measures of dysarthria. These findings indicate that axonal damage, particularly when measured using diffusion metrics, underpin dysarthria in multiple sclerosis.

Activation of Shh/Smo is sufficient to maintain oligodendrocyte precursor cells in an undifferentiated state and is not necessary for myelin formation and (re)myelination.

Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2 (control), Smofl/fl/NG2-CreERT2 (loss of function), and SmoM2/NG2-CreERT2 (gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (Smoothened Agonist (SAG) or cyclopamine treatment, respectively). To explore the effects of Shh/Smo on differentiation and myelination in vivo, we developed a highly quantifiable model by transplanting oligodendrocyte precursor cells (OPCs) in the retina. We find that myelination is greatly enhanced upon cyclopamine treatment and hypothesize that Shh/Smo could promote OPC proliferation to subsequently inhibit differentiation. Consistent with this hypothesis, we find that the genetic activation of Smo significantly increased numbers of OPCs and decreased oligodendrocyte differentiation when we examined the corpus callosum during development and after cuprizone demyelination and remyelination. However, upon loss of function with the conditional ablation of Smo, myelination in the same scenarios are unchanged. Taken together, our present findings suggest that the Shh pathway is sufficient to maintain OPCs in an undifferentiated state, but is not necessary for myelination and remyelination.