Brain Structures Research Articles

Bridging the gap: Prenatal nutrition, myelination, and schizophrenia etiopathogenesis

Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management.

Can a nature walk change your brain? Investigating hippocampal brain plasticity after one hour in a forest

In cities, the incidence of mental disorders is higher, while visits to nature have been reported to benefit mental health and brain function. However, there is a lack of knowledge about how exposure to natural and urban environments affects brain structure. To explore the causal relationship between exposure to these environments and the hippocampal formation, 60 participants were sent on a one hour walk in either a natural (forest) or an urban environment (busy street), and high-resolution hippocampal imaging was performed before and after the walks. We found that the participants who walked in the forest had an increase in subiculum volume, a hippocampal subfield involved in stress response inhibition, while no change was observed after the urban walk. However, this result did not withstand Bonferroni correction for multiple comparisons. Furthermore, the increase in subiculum volume after the forest walk was associated with a decrease in self-reported rumination. These results indicate that visits to nature can lead to observable alterations in brain structure, with potential benefits for mental health and implications for public health and urban planning policies.

Improved cognition and preserved hippocampal fractional anisotropy in subjects undergoing carotid endarterectomy “CEA preserves cognition & hippocampal structure”

ObjectivesA growing body of data indicates that extracranial carotid artery disease (ECAD) can contribute to cognitive impairment. However, there have been mixed reports regarding the benefit of carotid endarterectomy (CEA) as it relates to preserving cognitive function. In this work, diffusion magnetic resonance imaging (dMRI) and neurocognitive testing are used to provide insight into structural and functional brain changes that occur in subjects with significant carotid artery stenosis, as well as changes that occur in response to CEA. Materials and MethodsThe study design was a prospective, non-randomized, controlled study that enrolled patients with asymptomatic carotid stenosis. Thirteen subjects had severe ECAD (≥70% stenosis in at least one carotid artery) and were scheduled to undergo surgery. Thirteen had asymptomatic ECAD with <70% stenosis, therefore not requiring surgery. All subjects underwent neurocognitive testing using the Montreal Cognitive Assessment test (MoCA) and high angular resolution, multi-shell diffusion magnetic resonance imaging (dMRI) of the brain at baseline and at four-six months follow-up. Changes in MoCA scores as well as in Fractional anisotropy (FA) along the hippocampus were compared at baseline and follow-up. ResultsAt baseline, FA was significantly lower along the ipsilateral hippocampus in subjects with severe ECAD compared to subjects without severe ECAD. MoCA scores were lower in these individuals, but this did not reach statistical significance. At follow-up, MoCA scores increased significantly in subjects who underwent CEA and remained statistically equal in control subjects that did not have CEA. FA remained unchanged in the CEA group and decreased in the control group. ConclusionsThis study suggests that CEA improves cognition and preserves hippocampal white matter structure compared to control subjects not undergoing CEA.

Impact of environmental concentrations of fipronil on DNA integrity and brain structure of Bombus atratus bumblebees

Fipronil (FP) is an insecticide used in the treatment and control of pests, but it also adversely affects bees. Currently, there is no data on the genotoxic effects of FP in the brain of bumblebees. Thus, through the comet assay and routine morphological analysis, we analyzed the morphological effects and potential genotoxicity of environmentally relevant concentrations of FP on the brain of Bombus atratus. Bumblebees were exposed at concentrations of 2.5 μg/g and 3.5 μg/g for 96 hours. After the exposure, the brains were removed for morphological and morphometric analysis, and the comet assay procedure - used to detect DNA damage in individual cells using electrophoresis. Our data showed that both concentrations (2.5 μg/g and 3.5 μg/g) caused DNA damage in brain cells. These results corroborate the morphological data. We observed signs of synapse loss in the calyx structure, intercellular spaces between compact inner and non-compact inner cells, and cell swelling. This study provides unprecedented evidence of the effects of FP on DNA and cellular structures in the brain of B. atratus and reinforces the need to elucidate its toxic effects on other species to allow future risk assessments and conservation projects.

Preoperative early-stage lung cancer patients and local brain area changes: a cross-sectional observational descriptive study.

Lung cancer is a major global health concern. Patients undergo a substantial process of emotional transformation following a lung cancer diagnosis, during which subtle changes in brain function and/or structure may occur. As such, the present study aimed to investigate the neuroplastic changes induced by negative emotions in patients with early-stage lung cancer. This cross-sectional study recruited 35 patients with early-stage lung cancer and 33 age- and sex-matched healthy control patients. All participants completed the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and functional magnetic resonance imaging (fMRI). Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used as the fMRI indices. Correlations between the clinical assessments and ALFF and ReHo values were calculated. Our analysis revealed no significant differences in HAMD and HAMA scores between patients and control patients (p > 0.05). However, significant alterations in ALFF and ReHo were observed in multiple brain regions in patients with early-stage lung cancer compared to healthy controls (P FalseDiscoveryRate < 0.05). Specifically, ALFF values were decreased in the right postcentral gyrus, calcarine, and left middle cingulate, while ReHo values increased in the right angular gyrus and decreased in the bilateral postcentral gyrus, insula, left calcarine, putamen, superior temporal gyrus, middle cingulate, and right Rolandic gyrus. The HAMD score was significantly correlated with the ALFF value in the right postcentral gyrus (P = 0.007). This study provides valuable insights into the adaptive responses of the brain following the early diagnosis of lung cancer, revealing potential disturbances in negative emotional processing. Harnessing neuroplasticity may open new avenues for the establishment of personalized treatment strategies and targeted interventions to support the emotional and mental health of patients with lung cancer.

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

Conditional learning abilities in Down syndrome and Williams syndrome

ABSTRACT We investigated whether individuals with Down (DS) or Williams (WS) syndrome are capable of conditional learning, a hippocampus-dependent process enabling flexible reasoning, using three touch-screen tasks: a visual learning task to assess unconditional learning (A > B and C > D), a 3-item conditional learning task (A > B, B > C), and a 5-item conditional learning task (A > B, B > C, C > D, D > E) to further assess transitive inference abilities. We compared the performance of individuals with DS or WS to typically developing 3–12-year-old children and 20–30-year-old adults. Most participants exhibited unconditional learning, but only 12% of individuals with DS, 15% of individuals with WS, and 42% of children exhibited conditional learning, as compared to 95% of young adults; only adults demonstrated transitive inference. Our findings indicate that conditional learning and transitive inference, which depend on brain structures impacted in these disorders, including the hippocampus and the prefrontal cortex, are beyond reach for most individuals with DS and WS.

A Diffusion Tensor Imaging White Matter Atlas of the Domestic Canine Brain

Abstract There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts—including association, projection, commissural, brainstem, olfactory and cerebellar tracts—were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Osteoarthritis, osteoarthritis treatment and risk of incident dementia: a prospective cohort study based on UK Biobank.

We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.

Structure-function coupling in macroscale human brain networks.

Precisely how the anatomical structure of the brain gives rise to a repertoire of complex functions remains incompletely understood. A promising manifestation of this mapping from structure to function is the dependency of the functional activity of a brain region on the underlying white matter architecture. Here, we review the literature examining the macroscale coupling between structural and functional connectivity, and we establish how this structure-function coupling (SFC) can provide more information about the underlying workings of the brain than either feature alone. We begin by defining SFC and describing the computational methods used to quantify it. We then review empirical studies that examine the heterogeneous expression of SFC across different brain regions, among individuals, in the context of the cognitive task being performed, and over time, as well as its role in fostering flexible cognition. Last, we investigate how the coupling between structure and function is affected in neurological and psychiatric conditions, and we report how aberrant SFC is associated with disease duration and disease-specific cognitive impairment. By elucidating how the dynamic relationship between the structure and function of the brain is altered in the presence of neurological and psychiatric conditions, we aim to not only further our understanding of their aetiology but also establish SFC as a new and sensitive marker of disease symptomatology and cognitive performance. Overall, this Review collates the current knowledge regarding the regional interdependency between the macroscale structure and function of the human brain in both neurotypical and neuroatypical individuals.

Exploration of the white matter bundles connected to the pineal gland: A DTI study.

Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are reports on the role of this area for brain function by hormone secretion, as well as few reports on its role in brain cognition. However, little knowledge is available on the PG, and in particular on the structural connectivity of this region with the other brain structures. Using diffusion-weighted images collected by a 3T MRI scanner, and using a sample of 61 (29F) mentally and physically healthy young individuals in the age range of 20-30 years old, we tried to extract the white matter bundles connected to the PG. Based on prior knowledge, seven target bundles were suggested to be between the PG body and the PG roots, Pons, Periventricular region, thalamus, caudate, lentiform, suprachiasmatic nuclei, and the supercervical ganglia. Nearly all the target bundles were successfully extracted, with the exception of the lentiform. Rate of identification of the tracts was different, with the bundle between the PG body and roots having the highest identification rate (97%); then it was with the Pons (70%), Periventricular region (57%), SCN (55%), left thalamus (52%), right thalamus (47%), left caudate (27%) and right caudate (22%). This study is an attempt to expand our knowledge on the neuroanatomy of the PG, which might help for identifying further roles for it in brain functionality, and also be a help for the treatment of some disorders in the future.

Pituitary Apoplexy: a re-appraisal of risk factors and best management strategies in the COVID-19 era.

Pituitary apoplexy (PA) is a clinical syndrome caused by acute hemorrhage and/or infarction of the pituitary gland, most commonly in the setting of a pituitary macroadenoma. PA generally presents with severe headache, nausea, vomiting, visual disturbance, and, in more severe cases, altered mental status. Many factors have been attributed to the risk of developing PA, including most recently, numerous reports showcasing an association with COVID-19 infection or vaccination. Initial management of PA includes evaluation and correction of deficient hormones and electrolytes and an assessment if surgical decompression to relieve pressure on optic nerves and other brain structures is needed. While prompt recognition and treatment are crucial to avoid morbidity and mortality, in the modern era, PA is less commonly considered a true neurosurgical emergency requiring immediate (< 24h) surgical decompression. Traditionally, surgical decompression has been the standard of care for significant mass effects. However, several studies have shown similar outcomes in visual and hormonal recovery with either surgical decompression or conservative medical management. Unfortunately, most evidence on optimal management strategies is limited to retrospective case series, small prospective studies, and one multi-center observational study. This review aims to provide the most up-to-date evidence on the role of COVID-19 in PA and best management strategies.

The effects of musicality on brain network topology in the context of Alzheimer’s disease and memory decline

Abstract Music’s role in modulating brain structure, particularly in neurodegenerative contexts such as Alzheimer’s Disease (AD), has been increasingly recognized. While previous studies have hinted at the potential neuroplastic benefits of musical engagement and training, the mechanisms through which music impacts structural connectivity in neurodegenerative pathways remain underexplored. We aimed to examine the impact of music perception skills, active musical engagement, and musical training on structural connectivity in areas relating to memory, emotion, and learning in individuals with worsening memory impairment, investigating the potential neuroplastic effects of music. Employing diffusion tensor imaging (DTI) based structural connectivity and graph theoretical analysis, we investigated brain topological features in 78 participants aged 42 to 85 with a range of memory impairments. Participants were assessed for musical training, engagement, and perception skills. The study analyzed regional and local network topological metrics to examine the influence of musical activities on graph metrics, while controlling for stages of objective memory impairment (SOMI) and diagnosis, separately. This study aimed to elucidate the effects of musical perception skills, active musical engagement, and musical training on structural connectivity within memory, emotion, and learning-related brain areas in individuals with varying degrees of memory impairment. We found enhanced structural connectivity of the right hippocampus and the right posterior cingulate cortex was associated with stronger local network metrics, such as clustering coefficient and betweenness centrality, with increased music perception skills like melody and beat perception. Musical training specifically impacted the clustering coefficient of the right hippocampus and the node degree of the right mid cingulate gyrus. Active musical engagement influenced the eigenvector centrality of the right hippocampus. Furthermore, musical training was associated with enhanced global metrics, such as global efficiency and characteristic path length. Our study integrates diffusion magnetic resonance imaging (MRI) and graph theoretical analysis to reveal significant effects of musical activities on structural connectivity in key brain regions. The results highlight the potential of musical activities to serve as a non-invasive modulatory tool for cognitive resilience, especially in memory impairment and neurodegeneration contexts. These insights contribute to the understanding of delaying AD onset and aiding early-stage patients through music-based interventions, emphasizing the importance of musical engagement in maintaining cognitive and brain health.

Association of glycosylated hemoglobin concentrations with structural and functional brain changes in the normoglycemic population: A systematic review.

Optimal glucose control is crucial for maintaining brain health and preventing metabolic and cognitive disorders in the general population. Glycosylated hemoglobin (HbA1c) serves as a key marker for assessing glucose intolerance and its impact on brain structure and function in healthy individuals. However, existing literature presents conflicting findings, necessitating a systematic review to consolidate current knowledge in this domain. This systematic review examines 26 English-language studies involving participants aged 15 years and above, investigating the relationship between HbA1c levels and brain health. Studies focusing on normal/general populations and utilizing magnetic resonance imaging (MRI) as the imaging modality were included. Exclusion criteria encompassed review articles, abstracts, letters, animal studies, and research involving neuropsychiatric or metabolic diseases. Data were gathered from PubMed, Scopus, and Web of Science databases up to November 2023. Analysis reveals significant associations between HbA1c levels and various brain metrics, including volume, cortical thickness, fractional anisotropy, mean diffusivity, activity, and connectivity. However, findings exhibit inconsistency, likely attributed to disparities in sample characteristics and study sizes. Notably, hippocampal volume, white matter hyperintensity, and ventral attention network connectivity emerge as frequently affected structures and functions, mirroring trends observed in diabetic populations. Despite inconclusive evidence, glucose intolerance appears to exert considerable influence on select brain structures and functions in individuals without diagnosed metabolic disorders. Understanding these associations is critical for mitigating the risk of cognitive decline and dementia in healthy populations. Future investigations should aim to elucidate the intricate relationship between HbA1c concentrations and brain health parameters in normoglycemic individuals.

A real-time working memory evaluation system for macaques in microwave fields.

With the development and widespread application of electromagnetic technology, the health hazards of electromagnetic radiation have attracted much attention and concern. The effect of electromagnetic radiation on the nervous system, especially on learning, memory, and cognitive functions, is an important research topic in the field of electromagnetic biological effects. Most previous studies were conducted with rodents, which are relatively mature. As research has progressed, studies using non-human primates as experimental subjects have been carried out. Compared to rodents, non-human primates such as macaques not only have brain structures more similar to those of humans but also exhibit learning and memory processes that are similar. In this paper, we present a behavioral test system for the real-time evaluation of the working memory (WM) of macaques in a microwave environment. The system consists of two parts: hardware and software. The hardware consists of four modules: the operation terminal, the control terminal, the optical signal transmission, and detection module and the reward feedback module. The software program can implement the feeding learning task, the button-pressing learning task, and the delayed match-to-sample task. The device is useful for the real-time evaluation of the WM of macaques in microwave environments, showing good electromagnetic compatibility, a simple and reliable structure, and easy operation.

Causal association between brain structure and obstructive sleep apnea: A mendelian randomization study

ObjectivePrevious studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship. MethodsFirstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. ResultsThe results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates. ConclusionsThis study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity.

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an increase in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

Early intensive rehabilitation reverses locomotor disruption, decrease brain inflammation and induces neuroplasticity following experimental Cerebral Palsy

BackgroundCerebral Palsy (CP) is a major cause of motor and cognitive disability in children due to injury to the developing brain. Early intensive sensorimotor rehabilitation has been shown to change brain structure and reduce CP symptoms severity. We combined environmental enrichment (EE) and treadmill training (TT) to observe the effects of a one-week program of sensorimotor stimulation (EETT) in animals exposed to a CP model and explored possible mechanisms involved in the functional recovery. MethodsPregnant Wistar rats were injected with Lipopolysaccharide (LPS − 200 µg/kg) intraperitoneally at embryonic days 18 and 19. At P0, pups of both sexes were exposed to 20′ anoxia at 37 °C. From P2 to P21, hindlimbs were restricted for 16 h/day during the dark cycle. EETT lasted from P21 to P27. TT − 15 min/day at 7 cm/s. EE − 7 days in enriched cages with sensorimotor stimulus. Functional 3D kinematic gait analysis and locomotion were analyzed. At P28, brains were collected for ex-vivo MRI and histological assessment. Neurotrophins and key proteins involved in CNS function were assessed by western blotting. ResultsCP model caused gross and skilled locomotor disruption and altered CNS neurochemistry. EETT reversed locomotor dysfunction with minor effects over gait kinematics. EETT also decreased brain inflammation and glial activation, preserved myelination, upregulated BDNF signaling and modulated the expression of proteins involved in excitatory synaptic function in the brain and spinal cord. ConclusionsUsing this translational approach based on intensive sensorimotor rehabilitation, we highlight pathways engaged in the early developmental processes improving neurological recovery observed in CP.

Association of Arterial Stiffness Index and Brain Structure in the UK Biobank: A 10-Year Retrospective Analysis.

Arterial stiffening and changes in brain structure both occur with normal aging and can be exacerbated via acquired health conditions. While cross-sectional associations exist, the longitudinal relationship between arterial stiffness and brain structure remains unclear. In this study, we investigated 1) associations between baseline arterial stiffness index (ASI) and brain structure (global and regional grey matter volumes (GMV), white matter hyperintensities (WMH)) 10-years post-baseline (10.4±0.8 years) and 2) associations between the 10-year change in ASI from baseline and brain structure 10-years post-baseline in 650 healthy middle- to older-aged adults (53.4±7.5 years) from the UK Biobank. We observed significant associations between baseline ASI and GMV (p<0.001) and WMH (p=0.0036) 10-years post-baseline. No significant associations between 10-year change in ASI and brain structure (global GMV p=0.24; WMH volume p=0.87) were observed. There were significant associations of baseline ASI in 2 of 60 regional brain volumes analyzed (right posterior superior temporal gyrus p=0.001; left superior lateral occipital cortex p<0.001). Strong associations with baseline ASI, but not changes in ASI over 10-years, suggest arterial stiffness at the entry point of older adulthood is more impactful on brain structure 10-years later compared to age-related stiffening. Based on these associations, we suggest clinical monitoring and potential intervention for reducing arterial stiffness should occur in midlife to reduce vascular contributions to structural changes in the brain, supporting a healthy trajectory of brain aging. Our findings also support use of ASI as a surrogate for gold standard measures in showing overall relationships between arterial stiffness and brain structure.