Search

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Significance: Mueller matrix imaging (MMI) is a comprehensive form of polarization imaging useful for assessing structural changes. However, there is limited literature on the polarimetric properties of brain specimens, especially with multispectral analysis. Aim: We aim to employ multispectral MMI for an exhaustive polarimetric analysis of brain structures, providing a reference dataset for future studies and enhancing the understanding of brain anatomy for clinicians and researchers. Approach: A multispectral wide-field MMI system was used to measure six fresh lamb brain specimens. Multiple decomposition methods (forward polar, symmetric, and differential) and polarization invariants (indices of polarimetric purity and anisotropy coefficients) have been calculated to obtain a complete polarimetric description of the samples. A total of 16 labels based on major brain structures, including grey matter (GM) and white matter (WM), were identified. K-nearest neighbors classification was used to distinguish between GM and WM and validate the feasibility of MMI for WM identification. Results: As the wavelength increases, both depolarization and retardance increase, suggesting enhanced tissue penetration into deeper layers. Moreover, utilizing multiple wavelengths allowed us to track dynamic shifts in the optical axis of retardance within the brain tissue, providing insights into morphological changes in WM beneath the cortical surface. The use of multispectral data for classification outperformed all results obtained with single-wavelength data and provided over 95% accuracy for the test dataset. Conclusions: The consistency of these observations highlights the potential of multispectral wide-field MMI as a non-invasive and effective technique for investigating the brain's architecture. [ABSTRACT FROM AUTHOR]

The continuous softening behavior of the brain tissue, i.e., the softening in the primary loading path with an increase in deformation, is modeled in this work as a state of hyperelasticity up to the onset of failure. That is, the softening behavior is captured via a core hyperelastic model without the addition of damage variables and/or functions. Examples of the application of the model will be provided to extant datasets of uniaxial tension and simple shear deformations, demonstrating the capability of the model to capture the whole-range deformation of the brain tissue specimens, including their softening behavior. Quantitative and qualitative comparisons with other models within the brain biomechanics literature will also be presented, showing the clear advantages of the current approach. The application of the model is then extended to capturing the rate-dependent softening behavior of the tissue by allowing the parameters of the core hyperelastic model to evolve, i.e., vary, with the deformation rate. It is shown that the model captures the rate-dependent and softening behaviors of the specimens favorably and also predicts the behavior at other rates. These results offer a clear set of advantages in favor of the considered modeling approach here for capturing the quasi-static and rate-dependent mechanical properties of the brain tissue, including its softening behavior, over the existing models in the literature, which at best may purport to capture only a reduced set of the foregoing behaviors, and with ill-posed effects. [ABSTRACT FROM AUTHOR]

Introduction: Impact of antioxidant supplements on the health of patients with Alzheimer’s disease has not yet been clearly defined. Given that no study has been conducted so far to evaluate the effectiveness of vitamins C and E on the expression of Carbonyl Protein (CP) and Heat Shock 70 (HSP70) genes in rats with Alzheimer’s, this study aims to investigate the effect of an eight-week supplementation of vitamins C and E on the expression of CP and HSP70 in the brain tissue of rats with Alzheimer’s disease. Methods: In this experimental study, 28 rats with Alzheimer disease were injected with 10 mg/kg of trimethyltin and divided into four groups: patient control, sham (soluble vitamin E), Vitamin C, and Vitamin E (VE). Seven healthy rats were included in the control group to investigate the effects of disease induction on the variables under study. They were administered a daily supplement of 4 mg/kg of vitamin C and 30 mg/kg of vitamin E for eight weeks. After supplementation period, the groups were compared in terms of CP values and HSP70 gene expression. Data were analyzed by SPSS16 statistical software. Shapiro-Wilk test was used to check normality of the finding distributions. Effect of vitamin E and vitamin C supplementation was evaluated using one-way analysis of variance. Tukey's post hoc test was used to check the type of variable effects. A significant level of 0.05 was considered for all analyses. Results: Levels of carbonyl protein in both the vitamin C and vitamin E groups were significantly lower than those in the patient control group (P < 0.05). HSP70 levels in the vitamin C and E groups were significantly higher than those in the patient control group (P < 0.05). No significant difference was observed between vitamin C and E supplement groups (P > 0.05). Conclusion: Findings of this study suggest that both vitamin C and E exhibit similar antioxidant and cellular protective effects in the brain tissue of mice with Alzheimer’s disease. Given the impact of vitamins C and E on reducing carbonyl protein levels and increasing HSP70 levels in the hippocampal tissue of rats, it is recommended to explore the effects of these vitamins on other neurodegenerative disorders in future studies.

The effect of strain rate and temperature on the hyperelastic material stress–strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8‐noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress–strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of inhaled oxygen level on dynamic glucose enhanced (DGE) MRI in mouse brain tissue and CSF at 3 T. Methods: DGE data of brain tissue and CSF from mice under normoxia or hyperoxia were acquired in independent and interleaved experiments using on‐resonance variable delay multi‐pulse (onVDMP) MRI. A bolus of 0.15 mL filtered 50% D‐glucose was injected through the tail vein over 1 min during DGE acquisition. MRS was acquired before and after DGE experiments to confirm the presence of D‐glucose. Results: A significantly higher DGE effect under normoxia than under hyperoxia was observed in brain tissue (p = 0.0001 and p = 0.0002 for independent and interleaved experiments, respectively), but not in CSF (p > 0.3). This difference is attributed to the increased baseline MR tissue signal under hyperoxia induced by a shortened T1 and an increased BOLD effect. When switching from hyperoxia to normoxia without glucose injection, a signal change of ˜3.0% was found in brain tissue and a signal change of ˜1.5% was found in CSF. Conclusions: DGE signal was significantly lower under hyperoxia than that under normoxia in brain tissue, but not in CSF. The reason is that DGE effect size of brain tissue is affected by the baseline signal, which could be influenced by T1 change and BOLD effect. Therefore, DGE experiments in which the oxygenation level is changed from baseline need to be interpreted carefully. [ABSTRACT FROM AUTHOR]

Triazolium cyclodextrin click cluster (+CCC) is an ideal scaffold to specifically bind phosphoinositides (PIPs) via multivalent electrostatic interaction. A new enrichment material, triazolium cyclodextrin click cluster-magnetic agarose bead conjugate (+CCC-MAB), was synthesized and applied to the PIP enrichment of brain tissue. The enriched sample was analyzed using MALDI-TOF MS in negative ion mode without any derivatization. The PIP extract of brain tissue is known to contain abundant lipid interferences. By employing magnetic pull-down separation using +CCC-MAB, we effectively removed the weak-binding interferences in the PIP extract, thereby improving the signal-to-noise ratio (S/N) of the PIPs. Our +CCC-MAB-based PIP enrichment enabled us to analyze 16 PIP species in brain tissue. Six species with high S/N were assigned by MS/MS, while the remaining 10 species with low S/N were characterized by an empirical selection guide based on the biological relevance of PIPs. We conclude that +CCC-MAB-based PIP enrichment is a promising MALDI sample preparation method for specific PIP analysis in brain tissue. [ABSTRACT FROM AUTHOR]

The brain is the highest nerve center regulating physiological behaviors and functions. Brain tissue is a saturated porous material composed mainly of solid phase and liquid phase. Interactions between the solid phase, the liquid phase and the physiological environment (temperature in particular) are manifested in the coupled thermo-mechanical behaviors of brain tissue, and affected by internal temperature, seepage and stress fields. Characterization of the coupled thermo-mechanical behaviors of brain tissue is the key to understanding brain function and disease pathology. Firstly, the thermal and mechanical properties of brain tissue measured via different experimental methods were introduced, with a particular focus placed upon the effects of the strain rate and the temperature. Theoretical and numerical models describing the coupled thermo-mechanical behaviors of brain tissues were then summarized, including mechanical models, heat transfer models and coupled thermo-mechanical models. Finally, this important multidisciplinary field was summarized and prospected. [ABSTRACT FROM AUTHOR]

Although the brain is the most important organ in the human body, its thermo-mechanical coupling mechanism during cryogenic freezing remains unclear. A thermo-mechanical model for the cryogenic freezing of brain tissue was established, considering the special shape of the skull and brain, the cerebrospinal fluid, the cranial constraints, and the frost-heave effects. Analyses of the temperature field, the phase field, and the pressure field caused by the frost heave of the cerebrospinal fluid during freezing show that, the temperature of the cerebrospinal fluid remains unchanged during coagulation, while the maximum temperature difference within the brain tissue could reach 20 K. The solid-liquid phase interface is about 0.3 mm thick, and the driving velocity is about 0.09 mm/s. The maximum displacement of the brain tissue due to freezing is about 0.12 mm near the skull, and the pressure gradient at the solid-liquid interface is as high as 500 MPa/mm, while the pressure inside the solid and the CSF keeps almost unchanged. This study provides a theoretical support for the human brain cryopreservation strategy and the brain protection [ABSTRACT FROM AUTHOR]

It's crucial to understand the biomechanical properties of brain tissue to comprehend the potential mechanisms of traumatic brain injury. This study, distinct from homogeneous models, integrates axonal coupling in both axial and transverse compressive experiments within a continuum mechanics framework to capture its intricate mechanical behaviors. Fresh porcine brains underwent unconfined compression at strain rates of 0.001/s and 0.1/s to 0.3 strain, allowing for a comprehensive statistical analysis of the directional, regional, and strain-rate-dependent mechanical properties of brain tissue. The established constitutive model, fitted to experimental data, delineates material parameters providing intuitive insights into the stiffness of gray/white matter isotropic matrices and neural fibers. Additionally, it predicts the mechanical performance of white matter matrix and axonal fibers under compressive loading. Results reveal that gray matter is insensitive to loading direction, exhibiting insignificant stiffness variations within regions. White matter, however, displays no significant differences in mechanical properties under axial and transverse loading, with an overall higher average stress than gray matter and a more pronounced strain-rate effect. Stress-strain curves indicate that, under axial compression, white matter axons primarily resist the load before transitioning to a matrix-dominated response. Under transverse loading, axonal fibers exhibit weaker resistance to lateral pressure. The mechanical behavior of brain tissue is highly dependent on loading rate, region, direction, and peak strain. This study, by combining experimentation with phenomenological modeling, elucidates certain phenomena, contributing valuable insights for the development of precise computational models.

Abstract Background The purpose of the present study was to enhance the memory-boosting activity of the standardized hydroalcoholic Camellia sinensis extract (CSE) by the formation of nanophytosomes with Leciva S70 phospholipid. The central composite design was used to optimize the solvent evaporation method for the formulation of C. sinesis phytosomes (CSP). Results The optimized formulation had a mean particle size of 212.3 nm ± 0.39, PDI of 0.238 ± 0.0197, and zeta potential of −42.02 ± 0.995 mV. C. sinensis phytosome formation was confirmed by analytical techniques. The aqueous solubility of the developed CSP was 95.92 ± 0.31, which is 7.34 times greater than that of pure CSE (13.07 ± 0.19). CSP was found more effective than either pure CSE (26.42 ± 0.4654%) or the physical mixture (32.15 ± 0.4596%) in releasing the CSE from the formulation (72.16 ± 0.5248%). Acute toxicity study corroborated the safety of CSP in rats. CSP demonstrated a significant (p

Background. Determining changes in the content of monoamine neurotransmitters and their metabolites in brain structures is a necessary part of studying the pharmacodynamics of antiparkinsonian drugs. A method for the joint determination of norepinephrine, adrenaline, dopamine, serotonin, 5-hydroxyindole-3-acetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid in rat brain tissue has not previously been developed.The aim of the study. To develop and to validate a method for the quantitative determination of norepinephrine, adrenaline, dopamine, serotonin, 5-hydroxyindole3-acetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid in rat brain tissue using high-performance liquid chromatography in combination with tandem mass spectrometry (HPLC-MS/MS).Materials and methods. A method for determining monoamine mediators and their metabolites was developed using the HPLC-MS/MS method. Brain tissue homogenates were prepared using a mechanical hand-operated homogenizer. The effect of various antioxidants on the stability of norepinephrine, adrenaline, dopamine and 3,4-dihydroxyphenylacetic acid in the test samples was studied.Results. Chromatographic separation of sample components was carried out using two Synergi Max RP (20 × 2.0 mm, 2.5 µm) and Synergi Fusion RP 80Å (250 × 4.6 mm, 4 µm) chromatographic columns. Elution was carried out in a gradient mode using a mobile phase based on methanol and a 0.1% solution of formic acid in water. To prepare homogenate batches, the samples were diluted with a solution of internal standards in methanol. A 5% aqueous solution of ascorbic acid was chosen as an antioxidant stabilizer.Conclusion. The developed methodology has been fully validated and meets the requirements of Russian and international guidelines. The chosen stabilization method allows samples of brain homogenates to be stored for 30 days after collection.

Brain tissue is one of the softest parts of the human body, composed of white matter and grey matter. The mechanical behavior of the brain tissue plays an essential role in regulating brain morphology and brain function. Besides, traumatic brain injury (TBI) and various brain diseases are also greatly influenced by the brain's mechanical properties. Whether white matter or grey matter, brain tissue contains multiscale structures composed of neurons, glial cells, fibers, blood vessels, etc., each with different mechanical properties. As such, brain tissue exhibits complex mechanical behavior, usually with strong nonlinearity, heterogeneity, and directional dependence. Building a constitutive law for multiscale brain tissue using traditional function-based approaches can be very challenging. Instead, this paper proposes a data-driven approach to establish the desired mechanical model of brain tissue. We focus on blood vessels with internal pressure embedded in a white or grey matter matrix material to demonstrate our approach. The matrix is described by an isotropic or anisotropic nonlinear elastic model. A representative unit cell (RUC) with blood vessels is built, which is used to generate the stress-strain data under different internal blood pressure and various proportional displacement loading paths. The generated stress-strain data is then used to train a mechanical law using artificial neural networks to predict the macroscopic mechanical response of brain tissue under different internal pressures. Finally, the trained material model is implemented into finite element software to predict the mechanical behavior of a whole brain under intracranial pressure and distributed body forces. Compared with a direct numerical simulation that employs a reference material model, our proposed approach greatly reduces the computational cost and improves modeling efficiency. The predictions made by our trained model demonstrate sufficient accuracy. Specifically, we find that the level of internal blood pressure can greatly influence stress distribution and determine the possible related damage behaviors.

Epigenetics, a potential underlying pathogenic mechanism of neurodegenerative diseases, has been in the scope of several studies performed so far. However, there is a gap in regard to analyzing different forms of early-onset dementia and the use of Lymphoblastoid cell lines (LCLs). We performed a genome-wide DNA methylation analysis on sixty-four samples (from the prefrontal cortex and LCLs) including those taken from patients with early-onset forms of Alzheimer's disease (AD) and frontotemporal dementia (FTD) and healthy controls. A beta regression model and adjusted p-values were used to obtain differentially methylated positions (DMPs) via pairwise comparisons. A correlation analysis of DMP levels with Clariom D array gene expression data from the same cohort was also performed. The results showed hypermethylation as the most frequent finding in both tissues studied in the patient groups. Biological significance analysis revealed common pathways altered in AD and FTD patients, affecting neuron development, metabolism, signal transduction, and immune system pathways. These alterations were also found in LCL samples, suggesting the epigenetic changes might not be limited to the central nervous system. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs, we observed mainly a positive correlation. This study enhances our understanding of the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in earlier clinical phases than brain tissue. [ABSTRACT FROM AUTHOR]

The pia-arachnoid complex (PAC) tissue plays a vital role in upholding the physiological functionality of brain tissue and bolstering its capacity to withstand detrimental loads. However, the mechanical attributes of the PAC tissue remain inadequately comprehended and insufficiently explored. This investigation acquired the indentation response of the PAC tissue through large deformation dynamic indentation. The mechanical significance in the face of external loads of the PAC tissue was elucidated through the combination of finite element simulation and experiment. The findings demonstrated that the PAC tissue can augment the cortex's shear modulus and damping ratio, fortifying the brain tissue's resistance against deformation. Additionally, the outcomes revealed that the PAC tissue can curtail the maximum stress and strain within the brain tissue by 40% and 53%, respectively, when subjected to substantial local deformation. Furthermore, the PAC tissue can impede strain propagation to the cerebral cortex during relaxation. This inquiry furnished a fundamental dataset for characterizing the dynamic mechanical properties within finite element simulations and experimental explorations involving brain tissue. [ABSTRACT FROM AUTHOR]

Background: The purpose of the present study was to enhance the memory-boosting activity of the standardized hydroalcoholic Camellia sinensis extract (CSE) by the formation of nanophytosomes with Leciva S70 phospholipid. The central composite design was used to optimize the solvent evaporation method for the formulation of C. sinesis phytosomes (CSP). Results: The optimized formulation had a mean particle size of 212.3 nm ± 0.39, PDI of 0.238 ± 0.0197, and zeta potential of −42.02 ± 0.995 mV. C. sinensis phytosome formation was confirmed by analytical techniques. The aqueous solubility of the developed CSP was 95.92 ± 0.31, which is 7.34 times greater than that of pure CSE (13.07 ± 0.19). CSP was found more effective than either pure CSE (26.42 ± 0.4654%) or the physical mixture (32.15 ± 0.4596%) in releasing the CSE from the formulation (72.16 ± 0.5248%). Acute toxicity study corroborated the safety of CSP in rats. CSP demonstrated a significant (p < 0.05) reduction in escape and transferred latency on both days (15th and 16th) as compared to CSE, indicating the improvement of the memory-boosting activity. Furthermore, CSP-treated rats significantly improved acetylcholine (Ach) levels and brain tissue concentration compared with CSE. Moreover, the phytosomal formulation of CSP exhibited its rationality with an improvement of bioavailability by 3.21 folds compared with pure CSE. Conclusion: The presence of phospholipids in the CSP formulation and the formation of smaller particles may aid in crossing the blood–brain barrier, increasing brain tissue concentration and bioavailability. This, in turn, leads to an increase in memory-boosting activity. [ABSTRACT FROM AUTHOR]

Management of chronic subdural hematoma (cSDH) poses unique challenges and can be fraught with complications. Understanding the spatial relationships of cSDH to adjacent brain tissue and skull topography is critical for successful surgical treatment. The aim of this report is to highlight the feasibility and efficacy of a novel augmented reality (AR) overlay tool for surgical planning with technical description of two surgical cases using AR for surgical management of cSDH. This report describes a fiducial-less AR system for surgical planning of surgical evacuation of cSDH. The AR system was used to superimpose 3D anatomy onto the patients head to provide image guidance during two cases of evacuation. Imaging demonstrated convexity cSDH. A 3D model of the patient's anatomy was created and registered onto the patients' heads using a novel AR system. Surgical evacuation of the cSDH was completed in each case with surgical planning assisted by AR overlay. [ABSTRACT FROM AUTHOR]

To explore the radiobiological effects and related mechanisms of brain tissue after craniocerebral irradiation in young rats. Twenty-seven young male rats were randomly divided into high dose group (group C) (n=9), low dose group (group B) (n=9) and control group (group A) (n=9). The brains of rats in the group C were irradiated with 20Gy, while those in the group B were irradiated with 3Gy. The changes of body weight and organ index of rats in the three groups after craniocerebral irradiation were recorded. 1 w later, the rats were killed, the brain tissue was taken out, and the brain tissue sections were stained with hematoxylin and eosin. The migration ability was detected by cell scratch test, the levels of oxidative stress, inflammatory factors and apoptosis factors in brain tissue were observed, and the radiobiological effects and possible mechanism of brain injury were analyzed. At 3 d and 7 d after craniocerebral irradiation, the body weight of rats in the group B and group C was lower than that in the group A, and that in the group C was lower than that in the group B. Compared with the group A, the thymus and spleen organ index of the group B and the group C decreased and the decrease degree of the group C was greater than that of the group B. The normal nerve cells in the hippocampus of rats have large and round nucleoli, clear nucleoli and intact cell membrane. The pathological sections of the group B showed nerve cell injury, swelling, deformation, pale cytoplasm and tissue edema. The results of scratch test showed that the cell migration distance between the group B and the group C was larger than that in the group A at 24 h and 48 h, and the migration distance in the group C was larger than that in the group B. Compared with the group A, the serum superoxide dismutase activity decreased and the malondialdehyde content increased in the group B, while the superoxide dismutase activity and malondialdehyde content in the group C increased compared with the group B. Compared with the group A, the concentrations of tumour necrosis factor-alpha and interleukin-6 in the serum of the group B were increased, and these in the group C were higher than those of the group B. Compared with the group A, the apoptotic factors Bcl-2-associated X-protein and caspase-3 in the group B increased, while the content of B-cell lymphoma 2 decreased. Compared with the group B, the apoptotic factors Bcl-2-associated X-protein and caspase-3 increased and the content of B-cell lymphoma 2 decreased in the group C. Brain irradiation caused radiation-induced pathological damage to the brain tissue of young rats, resulting in weight loss and damage to immune organs in a dose-dependent manner. Its mechanism can be mediated by promoting inflammation, oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: Brain tissue immersed in cerebrospinal fluid often exhibits complex mechanical behaviour, especially the nonlinear stress-strain and rate-dependent responses. Despite extensive research into its material properties, the impact of solution environments on the mechanical behaviour of brain tissue remains limited. This knowledge gap affects the biofidelity of head modelling. This study aimed to investigate the effect of solution environments on brain tissue under quasistatic and dynamic loading conditions. Methods: Porcine brain tissue was characterized in compression through quasi-static nonlinear testing and Dynamic Mechanical Analysis under various environments: air, physiological saline and artificial cerebrospinal fluid. Frequencies from 0.1 to 40 Hz were applied to determine dynamic behaviour, while brain samples were compressed up to a 0.3 strain level to obtain nonlinear response. The effects of strain, frequency and solution environment on the mechanical response of brain tissue were statistically evaluated. Results: As environmental conditions transitioned from air to artificial cerebrospinal fluid, the average stress of brain tissue increased by approximately 1.3, 1.3 and 1.4 times at strain levels of 0.1, 0.2 and 0.3, respectively. A statistically significant increase in dynamic storage and loss moduli was observed between air and artificial cerebrospinal fluid environments. At frequencies above 18 Hz, the tan delta in air was significantly lower. Conclusions: The mechanical characterization of brain tissue exhibited a dependency on solution environment under both quasi-static and dynamic loading conditions. Brain tissue showed higher stress levels and dynamic modulus in solution environments compared to an air environment. The results of this study are valuable for improving head simulations and brain material models. [ABSTRACT FROM AUTHOR]

Increased incidence of traumatic brain injury (TBI) imposes a growing need to understand the pathology of brain trauma. A correlation between the incidence of multiple brain traumas and rates of behavioural and cognitive deficiencies has been identified amongst people that experienced multiple TBI events. Mechanically, repetitive TBIs may affect brain tissue in a similar way to cyclic loading. Hence, the potential susceptibility of brain tissue to mechanical fatigue is of interest. Although temporal changes in ovine brain tissue viscoelasticity and biological fatigue of other tissues such as tendons and arteries have been investigated, no methodology currently exists to cyclically load ex vivo brain tissue. A novel rheology-based approach found a consistent, initial stiffening response of the brain tissue before a notable softening when subjected to a subsequential cyclic rotational shear. History dependence of the mechanical properties of brain tissue indicates susceptibility to mechanical fatigue. Results from this investigation increase understanding of the fatigue properties of brain tissue and could be used to strengthen therapy and prevention of TBI, or computational models of repetitive head injuries. [ABSTRACT FROM AUTHOR]

Finite element head models offer great potential to study brain-related injuries; however, at present may be limited by geometric and material property simplifications required for continuum-level human body models. Specifically, the mechanical properties of the brain tissues are often represented with simplified linear viscoelastic models, or the material properties have been optimized to specific impact cases. In addition, anatomical structures such as the arachnoid complex have been omitted or implemented in a simple lumped manner. Recent material test data for four brain regions at three strain rates in three modes of loading (tension, compression, and shear) was used to fit material parameters for a hyper-viscoelastic constitutive model. The material model was implemented in a contemporary detailed head finite element model. A detailed representation of the arachnoid trabeculae was implemented with mechanical properties based on experimental data. The enhanced head model was assessed by re-creating 11 ex vivo head impact scenarios and comparing the simulation results with experimental data. The hyper-viscoelastic model faithfully captured mechanical properties of the brain tissue in three modes of loading and multiple strain rates. The enhanced head model showed a high level of biofidelity in all re-created impacts in part due to the improved brain-skull interface associated with implementation of the arachnoid trabeculae. The enhanced head model provides an improved predictive capability with material properties based on tissue level data and is positioned to investigate head injury and tissue damage in the future. [ABSTRACT FROM AUTHOR]

The brain is an important part of the mammalian nervous system, is highly sensitive to hypoxia, and plays an important role in the adaptation of the body to hypoxic environments. This study was conducted to analyse the distribution and expression of hypoxia-related factors (hypoxia-inducible factor 1α, HIF-1α; erythropoietin, EPO; vascular endothelial growth factor, VEGF; vascular cell adhesion molecule, VCAM) in the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina in yaks of different ages (4d, 6-months-old and adult). Paraffin sections were obtained from the cerebellum, cerebrum, medulla oblongata, and corpora quadrigemina of healthy yak for 4-day-old, 6-months-old and adult yaks. Histological characteristics were assessed by haematoxylin staining. Immunohistochemical staining was performed to detect the distribution and expression of HIF-1α, EPO, VEGF and VCAM proteins. Immunohistochemical results showed that HIF-1α, EPO, VEGF, and VCAM were expressed in the pyramidal cell layer of the yak cerebrum, and distributed in the cerebellum granulose cell layer, Purkinje cell layer and medulla layer, and were mainly positive in Purkinje cells and medulla. It is expressed in the cell bodies of the medulla oblongata and the quadrimatous neurons. The expression level in the medulla oblongata was higher, indicating may play a crucial role in functional cohesion. The expression of HIF-1α in 4 d cerebellar tissues was higher than that in other age groups, and the expression of HIF-1α in the medulla oblongata increased with age. In addition, the expression levels of EPO and VEGF in the 6-month-old group were slightly higher than those in the other age groups. It is speculated that EPO and VEGF have obvious protective effects on brain tissue in the 6-month-old age group; VCAM showed no significant differences in the cerebrum, cerebellum, medulla oblongata, or corpora quadrigemina of the yaks. This study provides basic data for further exploration of the adaptive mechanism of plateau yak brain tissue. [ABSTRACT FROM AUTHOR]

Tris (2-chloroethyl) phosphate (TCEP) is a crucial organophosphorus flame retardant widely used in many industrial and commercial products. Available reports reported that TCEP could cause various toxicological effects on organisms, including humans. Unfortunately, toxicity data for TCEP (particularly on neurotoxicity) on aquatic organisms are lacking. In the present study, Danio rerio were exposed to different concentrations of TCEP for 42 days (chronic exposure), and oxidative stress, neurotoxicity, sodium, potassium-adenosine triphosphatase (Na+, K+-ATPase) activity, and histopathological changes were evaluated in the brain. The results showed that TCEP (100 and 1500 µg L−1) induced oxidative stress and significantly decreased the activities of antioxidant enzymes (SOD, CAT and GR) in the brain tissue of zebrafish. In contrast, the lipid peroxidation (LPO) level was increased compared to the control group. Exposure to TCEP inhibited the acetylcholinesterase (AChE) and Na+,K+-ATPase activities in the brain tissue. Brain histopathology after 42 days of exposure to TCEP showed cytoplasmic vacuolation, inflammatory cell infiltration, degenerated neurons, degenerated purkinje cells and binucleate. Furthermore, TCEP exposure leads to significant changes in dopamine and 5-HT levels in the brain of zebrafish. The data in the present study suggest that high concentrations of TCEP might affect the fish by altering oxidative balance and inducing marked pathological changes in the brain of zebrafish. These findings indicate that chronic exposure to TCEP may cause a neurotoxic effect in zebrafish. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of brain tumor is a serious event for the affected patient. Surgical resection is a crucial part in the treatment of brain tumors. However, the distinction between tumor and brain tissue can be difficult, even for experienced neurosurgeons. This is especially true in the case of gliomas. In this project we examined whether the biomechanical parameters elasticity and stress relaxation behavior are suitable as additional differentiation criteria between tumorous (glioblastoma multiforme; glioblastoma, IDH-wildtype; GBM) and non-tumorous, peritumoral tissue. Methods: Indentation measurements were used to examine non-tumorous human brain tissue and GBM samples for the biomechanical properties of elasticity and stress-relaxation behavior. The results of these measurements were then used in a classification algorithm (Logistic Regression) to distinguish between tumor and non-tumor. Results: Differences could be found in elasticity spread and relaxation behavior between tumorous and non-tumorous tissue. Classification was successful with a sensitivity/recall of 83% (sd = 12%) and a precision of 85% (sd = 9%) for detecting tumorous tissue. Conclusion: The findings imply that the data on mechanical characteristics, with particular attention to stress relaxation behavior, can serve as an extra element in differentiating tumorous brain tissue from non-tumorous brain tissue. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are extremely versatile naturally occurring membrane particles that convey complex signals between cells. EVs of different cellular sources are capable of inducing striking therapeutic responses in neurological disease models. Differently from pharmacological compounds that act by modulating defined signalling pathways, EV-based therapeutics possess multiple abilities via a variety of effectors, thus allowing the modulation of complex disease processes that may have very potent effects on brain tissue recovery. When applied in vivo in experimental models of neurological diseases, EV-based therapeutics have revealed remarkable effects on immune responses, cell metabolism and neuronal plasticity. This multimodal modulation of neuroimmune networks by EVs profoundly influences disease processes in a highly synergistic and context-dependent way. Ultimately, the EV-mediated restoration of cellular functions helps to set the stage for neurological recovery. With this review we first outline the current understanding of the mechanisms of action of EVs, describing how EVs released from various cellular sources identify their cellular targets and convey signals to recipient cells. Then, mechanisms of action applicable to key neurological conditions such as stroke, multiple sclerosis and neurodegenerative diseases are presented. Pathways that deserve attention in specific disease contexts are discussed. We subsequently showcase considerations about EV biodistribution and delineate genetic engineering strategies aiming at enhancing brain uptake and signalling. By sketching a broad view of EV-orchestrated brain plasticity and recovery, we finally define possible future clinical EV applications and propose necessary information to be provided ahead of clinical trials. Our goal is to provide a steppingstone that can be used to critically discuss EVs as next generation therapeutics for brain diseases. [ABSTRACT FROM AUTHOR]

Pulsed electric fields are extensively utilized in clinical treatments, such as subthalamic deep brain stimulation, where electric field loading is in direct contact with brain tissue. However, the alterations in brain tissue's mechanical properties and microstructure due to changes in electric field parameters have not received adequate attention. In this study, the mechanical properties and microstructure of the brain tissue under pulsed electric fields were focused on. Herein, a custom indentation device was equipped with a module for electric field loading. Parameters such as pulse amplitude and frequency were adjusted. The results demonstrated that following an indentation process lasting 5 s and reaching a depth of 1000 μm, and a relaxation process of 175 s, the average shear modulus of brain tissue was reduced, and viscosity decreased. At the same amplitude, high-frequency pulsed electric fields had a smaller effect on brain tissue than low-frequency ones. Furthermore, pulsed electric fields induced cell polarization and reduced the proteoglycan concentration in brain tissue. As pulse frequency increased, cell polarization diminished, and proteoglycan concentration decreased significantly. High-frequency pulsed electric fields applied to brain tissue were found to reduce impedance fluctuation amplitude. This study revealed the effect of pulsed electric fields on the mechanical properties and microstructure of ex vivo brain tissue, providing essential information to promote the advancement of brain tissue electrotherapy in clinical settings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model, high-sugar and high-fat dietinduced model and spontaneous animal model. Establishing a simple, easy, short-cycle, safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE: To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS: Twenty Sprague-Dawley rats were randomly divided into control (n=10) and model (n=10) groups. Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity, and those in the control group were given the same amount of citrate buffer. During the experiment, the body mass, feed intake, water intake and blood glucose were measured. After 8 weeks, the glucose tolerance and oxidative stress levels were measured, and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION: Compared with the control group, the food intake, water intake, encephalization quotient, blood glucose and area under the blood glucose curve were significantly increased in the model group, while the body mass decreased significantly (P < 0.01). Histopathological examination of the brain showed that compared with the control group, the number of surviving nerve cells was significantly reduced in the model group (P < 0.01), with more significant pathological damage of nerve cells. Compared with the control group, the activities of serum superoxide dismutase, catalase and glutathione in the model group were significantly decreased (P < 0.01), and the content of oxidative malondialdehyde was significantly increased (P < 0.05). The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group, while the expression of Bcl-2 decreased (P < 0.01). In conclusion, an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats, to successfully establish the rat model of diabetic encephalopathy. [ABSTRACT FROM AUTHOR]

The activities of HIV‐1 in the central nervous system (CNS) are responsible for a dysregulated neuroinflammatory response and the subsequent development of HIV‐associated neurocognitive disorders (HAND). The use of post‐mortem human brain tissue is pivotal for studying the neuroimmune mechanisms of CNS HIV infection. To date, numerous studies have investigated HIV‐1‐induced neuroinflammation in post‐mortem brain tissue. However, from the commonly investigated studies in this line of research, it is not clear which neuroinflammatory markers are consistently associated with HIV neurocognitive impairment (NCI) and neuropathology (i.e., HIV‐encephalitis, HIVE). Therefore, we conducted a systematic review of the association between neuroinflammation and NCI/HIVE from studies investigating post‐mortem brain tissue. Our aim was to synthesise the published data to date to provide commentary on the most noteworthy markers that are associated with NCI/HIVE. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Sixty‐one studies were included that investigated the levels of inflammatory markers based on their gene and protein expression in association with NCI/HIVE. The findings revealed that the (1) transcript expressions of IL‐1β and TNF‐α were consistently associated with NCI/HIVE, whereas CCL2 and IL‐6 were commonly not associated with NCI/HIVE, (2) protein expressions of CD14, CD16, CD68, Iba‐1, IL‐1β and TNF‐α were consistently associated with NCI/HIVE, while CD45, GFAP, HLA‐DR, IL‐1 and IL‐6 were commonly not associated with NCI/HIVE, and (3) gene and protein expressions of CNS IL‐1β and TNF‐α were consistently associated with NCI/HIVE, while IL‐6 was consistently not associated with NCI/HIVE. These markers highlight the commonly investigated markers in this line of research and elucidates the neuroinflammatory mechanisms in the HIV‐1 brain that are involved in the pathophysiology of NCI/HIVE. These markers and related pathways should be investigated for the development of improved diagnostics, prognostics, and therapeutics of HAND. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) is a promising tool for intraoperative tissue morphology determination. Several studies suggest that attenuation coefficient derived from the OCT images, can differentiate between tissues of different morphology, such as normal and pathological structures of the brain, skin, and other tissues. In the present study, the depth‐resolved method for attenuation coefficient calculation was adopted for the real‐world situation of the depth‐dependent OCT sensitivity and additive imaging noise with nonzero mean. It was shown that in the case of sharp focusing (~10 μm spot full width at half maximum [FWHM] or smaller at 1.3 μm central wavelength) only the proposed method for depth‐dependent sensitivity compensation does not introduce misleading artifacts into the calculated attenuation coefficient distribution. At the same time, the scanning beam focus spot with FWHM greater than 10 μm at 1.3 μm central wavelength allows one to use multiple approaches to the attenuation coefficient calculation without introducing noticeable bias. This feature may hinder the need for robust corrections for the depth‐resolved attenuation coefficient estimations from the community. [ABSTRACT FROM AUTHOR]

A simple exponential model of diffuse reflectance for a two-layered medium was developed theoretically based on Monte Carlo simulation. Absorption and reduced scattering coefficients of these two layers were chosen to be different in which scattering property was dominant and the reduced albedo of the upper layer ranged from 0.8 to 0.99 and from 0.93 to 0.98 for the lower layer. Furthermore, the refractive index and anisotropy factor of these two layers were assumed to be equal 1.4 and 0.9 respectively. On the other hand, a finite element method was used to solve a diffusion approximation via COMSOL Multiphysics environment to compare the developed model with a diffusion approximation. The presented model has shown a low relative error, which did not exceed 20%. That was lower than the diffusion approximation results and it was in accordance with another complicated model developed by another research group. Consequently, the robustness of the presented model makes it more likely to predict a reflectance and reproduce the model to estimate a top layer thickness in real-time.

Mechanical properties of brain tissues are from principal features from different points of view; diagnosis, the performance of the brain and neurological disorders. Particularly viscoelastic properties of the brain tissues are determinative. In this study based on a proposed accurate and non-invasive method, we have measured the viscoelastic properties of prefrontal cortex and cerebellum, two important brain regions involved in motor learning and pathophysiology of autism spectrum disorder (ASD). In this regard, using photoacoustic systems, viscoelastic properties of tissues from the cerebellum and prefrontal cortex of normal and prenatal VPA (Valproic acid)-exposed (i.e. autistic-like) offspring rats are measured. Results of our study show that the cerebellums of normal tissues are stiffer than the tissue obtained from autistic-like rats, while the viscoelasticity of the prefrontal cortex of normal tissues is higher than that of autistic ones. The proposed method for the measurement of viscoelastic properties of the brain tissue has the potential not only for the fundamental studies but as a diagnosis technique.

A systematic analysis of scientific research devoted to the study of neuroprotective properties of xenon was carried out to determine the possibility of its use for the protection of neuronal tissues in various pathological conditions and neurodegenerative disorders. The search was carried out in freely available scientometric databases, such as PubMed, Google Scholar, Web of Science, Scopus, etc. The criteria for inclusion in the analysis were publications that discussed the role of xenon in the protection of neuronal tissues, studies of the neuroprotective properties of xenon in animal and cellular models, clinical studies demonstrating the neuroprotective potential of xenon in available English-language sources. The literature was analyzed to identify key findings, research methodology, and outcomes related to the neuroprotective properties of xenon. This included an analysis of research methods, models used to assess the impact of xenon on neuronal structures, and the volume and quality of the data obtained. In addition, the pharmacological properties of xenon are considered, in particular, its physicochemical characteristics, mechanisms of action at the molecular level, and pharmacokinetics. The results of studies of the influence of xenon on the state of vascularization of the brain after after traumatic brain injury and the potential of xenon to prevent further injuries are presented. Studies evaluating the effects of xenon on neurological deficits after ischemic stroke and its potential efficacy as an anti-inflammatory and neuroprotective agent are discussed. The effect of xenon on the white matter of the brain in patients with aneurysmal subarachnoid hemorrhage and its potential to reduce damage are highlighted. Research data on the use of the liposomal form of xenon to improve the condition after a stroke, mental health, and the effect of xenon on the intestinal microbiota were analyzed. The results of studies on the effectiveness of repeated injections of xenon to improve sensorimotor and neuropsychic functions in patients after a stroke, as well as the use of xenon as one of the components of intensive therapy for alcohol poisoning and the potential advantages of such an approach are presented. Based on the analysis of literary sources, it was concluded that xenon is a promising tool for protecting brain structures in traumatic injuries and ischemic lesions, which improves rehabilitation. It reduces inflammation and increases the integrity of the blood-brain barrier, which helps restore brain function.

This scientific commentary discusses the role of glial fibrillary acidic protein (GFAP) as a biomarker for astrocyte reactivity in Alzheimer's disease. The authors reference a study that measured serum GFAP levels in individuals with dementia and found a significant correlation between GFAP levels and the severity of Alzheimer's disease neuropathology. They also tested the association between serum GFAP and brain tissue GFAP immunostaining, finding a positive correlation in the superior entorhinal cortex. The authors suggest that blood GFAP could serve as a prognostic biomarker for Alzheimer's disease and other neurodegenerative disorders. [Extracted from the article]

Background Little is known about the distribution of posaconazole in brain tissue and CSF. We therefore analysed trough concentrations of posaconazole in paediatric leukaemia patients in non-inflamed CSF. Patients and methods The study included paediatric patients <18 years of age with acute leukaemia in remission who underwent repeat therapeutic lumbar punctures as part of their anti-leukaemia treatment. CSF and blood were obtained 20–24 h after dosing, and posaconazole was measured by LC-MS/MS. Results Six patients (median age: 10 years; range, 6–14) with acute lymphatic (three) or acute myeloid (three) leukaemia were included who received posaconazole gastroresistant tablets at weight-banded doses (five) or the oral solution (one). In contrast to 14 control samples, posaconazole was detectable in all 11 samples of treated patients. CSF concentrations ranged from 8.3 to 42 ng/mL with a median CSF concentration of 13.6 ng/mL. Concurrent serum concentrations were between 965 and 5177 ng/mL with a median of 1716 ng/mL. Conclusions Trough concentrations of posaconazole in the CSF after systemic administration were low but detectable in all subjects. Concurrent serum concentrations were in the target range for prophylaxis and treatment in 100% and 90%, respectively. [ABSTRACT FROM AUTHOR]

Delaying aging has become a hot spot of social concern and research. Our previous studies have shown that ripe Pu-erh tea can delay aging in mice by regulating the intestinal flora, but the metabolites in response to endogenous substances in mice are not clear. In this paper, the Morris water maze test was used to detect learning and memory capacity in control, D-galactose-induced aging, and ripe Pu-erh tea-treated mice. Non-targeted metabolomics was used to detect metabolites in the brain tissue and serum of mice from each group for the purpose of exploring the anti-aging effect of ripe Pu-erh tea on D-galactose-induced aging mice, screening differential metabolites among the three groups and analyzing the related metabolic pathways. The results showed that ripe Pu-erh tea improved learning capacity, and regulated 26 differential metabolites in the brain tissue of aging mice, mainly involved in the glycerophospholipid metabolism, vitamin B6 metabolism, histidine metabolism and purine metabolism pathways, among which the glycerophospholipid metabolism and histidine metabolism pathway were the most significant. A total of 11 differential metabolites were identified in serum, mainly involved in the metabolism of vitamin B6 and arachidonic acid, among which vitamin B6 metab olism pathway was the most significant. After the intervention with ripe Pu-erh tea, the contents of glycerophospholipid metabolites including phosphatidylcholine [PC (20:5/20:4)], phosphatidyl ethanlamine [PE (22:2/14:0)], phosphatidylserine [PS (20:5/18:1)] and lysophosphatidylcholine [LysoPC (18:2)], the histidine metabolite carnosine, and the vitamin B6 metabolite pyridoxal 5’-phosphate were significantly increased in aging mice. These results suggest that ripe Pu-erh tea can delay aging by regulating lipid and amino acid metabolism.

Background and Aim: Social isolation stress (SIS) and individual housing have been shown to cause abnormal cognitive insufficiencies, altered anxiety levels, and signs of psychiatric diseases. Acorus calamus (AC), commonly known as Sweet Flag, has been widely used in India to treat neurological, metabolic, and respiratory disorders, indicating its potential therapeutic value. This study aimed to determine the antidepressant and antioxidative effects of AC on rats subjected to long-term, social-isolation-induced stress. Materials and Methods: This study involved 2-month-old male rats (24) weighing approximately 180200 g bred in-house. The rats were divided into four groups (n = 6): Group-1 received saline, Group-2 received SIS, Group-3 received only 50mg/kg AC, and Group-4 received 50mg/kg AC and SIS for 6 weeks. After this, behavioral, biochemical, and neuronal assay was conducted. Results: Behavioral experiments showed significantly higher activity levels (p < 0.001) in AC-treated rats than in the SIS group. In addition, rats subjected to SIS with AC treatment exhibited enhanced total antioxidants, superoxide dismutase, and neuronal assays compared to rats subjected to SIS alone. Conclusion: Acorus calamus treatment improved the antidepressant and antioxidant potential against SIS in rat brain tissue. Moreover, we proved that AC can effectively reverse the neurotoxicity induced by SIS in animal models. As we battle against the coronavirus disease 2019 pandemic and social isolation, AC could be considered a supplementary treatment to alleviate depressive-like symptoms in oBackground and Aim: Social isolation stress (SIS) and individual housing have been shown to cause abnormal cognitive insufficiencies, altered anxiety levels, and signs of psychiatric diseases. Acorus calamus (AC), commonly known as Sweet Flag, has been widely used in India to treat neurological, metabolic, and respiratory disorders, indicating its potential therapeutic value. This study aimed to determine the antidepressant and antioxidative effects of AC on rats subjected to long-term, social-isolation-induced stress. Materials and Methods: This study involved 2-month-old male rats (24) weighing approximately 180200 g bred in-house. The rats were divided into four groups (n = 6): Group-1 received saline, Group-2 received SIS, Group-3 received only 50mg/kg AC, and Group-4 received 50mg/kg AC and SIS for 6 weeks. After this, behavioral, biochemical, and neuronal assay was conducted. Results: Behavioral experiments showed significantly higher activity levels (p < 0.001) in AC-treated rats than in the SIS group. In addition, rats subjected to SIS with AC treatment exhibited enhanced total antioxidants, superoxide dismutase, and neuronal assays compared to rats subjected to SIS alone. Conclusion: Acorus calamus treatment improved the antidepressant and antioxidant potential against SIS in rat brain tissue. Moreover, we proved that AC can effectively reverse the neurotoxicity induced by SIS in animal models. As we battle against the coronavirus disease 2019 pandemic and social isolation, AC could be considered a supplementary treatment to alleviate depressive-like symptoms in our present-day lifestyle.

Background: Diabetic neuropathy is a debilitating manifestation of long-term diabetes mellitus. The present study explored the effects of the roots of Rubia cordifolia L. (R. cordifolia L.) in the Wistar rat model for diabetic neuropathy and possible neuroprotective, antidiabetic, and analgesic mechanisms underlying this effect. Materials and Methods: Rats were divided into five experimental groups. An amount of 0.25% carboxy methyl cellulose (CMC) in saline and streptozotocin (STZ) (60 mg/kg) was given to group 1 and group 2, respectively. Group 3 was treated with STZ and glibenclamide simultaneously while groups 4 and 5 were simultaneously treated with STZ and hydroalcoholic extract of the root of R. cordifolia, respectively. Hot plate and cold allodynias were used to evaluate the pain threshold. The antioxidant effects of R. cordifolia were assessed by measuring Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). At the end of the study, sciatic nerve and brain tissues were collected for histopathological study. Bcl-2 proteins, cleaved caspase-3, and Bax were assessed through the Western blot method. Results: R. cordifolia significantly attenuated paw withdrawal and tail flick latency in diabetic neuropathic rats. R. cordifolia significantly (p < 0.01) improved the levels of oxidative stress. It was found to decrease blood glucose levels and to increase animal weight in R. cordifolia-treated groups. Treatment with R. cordifolia suppressed the cleaved caspase-3 and reduced the Bax:Bcl2 ratio in sciatic nerve and brain tissue compared to the diabetic group. Histopathological analysis also revealed a marked improvement in architecture and loss of axons in brain and sciatic nerve tissues at a higher dose of R. cordifolia (400 mg/kg). Conclusion: R. cordifolia attenuated diabetic neuropathy through its antidiabetic and analgesic properties by ameliorating apoptosis and oxidative stress. [ABSTRACT FROM AUTHOR]

BackgroundFluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism.ObjectiveTo study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability.MethodsNinety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content

Epigenetics, a potential underlying pathogenic mechanism of neurodegenerative diseases, has been in the scope of several studies performed so far. However, there is a gap in regard to analyzing different forms of early-onset dementia and the use of Lymphoblastoid cell lines (LCLs). We performed a genome-wide DNA methylation analysis on sixty-four samples (from the prefrontal cortex and LCLs) including those taken from patients with early-onset forms of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) and healthy controls. A beta regression model and adjusted p-values were used to obtain differentially methylated positions (DMPs) via pairwise comparisons. A correlation analysis of DMP levels with Clariom D array gene expression data from the same cohort was also performed. The results showed hypermethylation as the most frequent finding in both tissues studied in the patient groups. Biological significance analysis revealed common pathways altered in AD and FTD patients, affecting neuron development, metabolism, signal transduction, and immune system pathways. These alterations were also found in LCL samples, suggesting the epigenetic changes might not be limited to the central nervous system. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs, we observed mainly a positive correlation. This study enhances our understanding of the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in earlier clinical phases than brain tissue.

Increased incidence of traumatic brain injury (TBI) imposes a growing need to understand the pathology of brain trauma. A correlation between the incidence of multiple brain traumas and rates of behavioural and cognitive deficiencies has been identified amongst people that experienced multiple TBI events. Mechanically, repetitive TBIs may affect brain tissue in a similar way to cyclic loading. Hence, the potential susceptibility of brain tissue to mechanical fatigue is of interest. Although temporal changes in ovine brain tissue viscoelasticity and biological fatigue of other tissues such as tendons and arteries have been investigated, no methodology currently exists to cyclically load ex vivo brain tissue. A novel rheology-based approach found a consistent, initial stiffening response of the brain tissue before a notable softening when subjected to a subsequential cyclic rotational shear. History dependence of the mechanical properties of brain tissue indicates susceptibility to mechanical fatigue. Results from this investigation increase understanding of the fatigue properties of brain tissue and could be used to strengthen therapy and prevention of TBI, or computational models of repetitive head injuries.

Background and Aim: Social isolation stress (SIS) and individual housing have been shown to cause abnormal cognitive insufficiencies, altered anxiety levels, and signs of psychiatric diseases. Acorus calamus (AC), commonly known as Sweet Flag, has been widely used in India to treat neurological, metabolic, and respiratory disorders, indicating its potential therapeutic value. This study aimed to determine the antidepressant and antioxidative effects of AC on rats subjected to long-term, social isolation-induced stress. Materials and Methods: This study involved 2-month-old male rats (24) weighing approximately 180–200 g bred in-house. The rats were divided into four groups (n = 6): Group 1 received saline, Group 2 received SIS, Group 3 received only 50 mg/kg AC, and Group 4 received 50 mg/kg AC and SIS for 6 weeks. After this, behavioral, biochemical, and neuronal assays were conducted. Results: Behavioral experiments showed significantly higher activity levels (p < 0.001) in AC-treated rats than in the SIS group. In addition, rats subjected to SIS with AC treatment exhibited enhanced total antioxidants, superoxide dismutase, and neuronal assays compared to rats subjected to SIS alone. Conclusion: Acorus calamus treatment improved the antidepressant and antioxidant potential against SIS in rat brain tissue. Moreover, we proved that AC can effectively reverse the neurotoxicity induced by SIS in animal models. As we battle against the coronavirus disease 2019 pandemic and social isolation, AC could be considered a supplementary treatment to alleviate depressive-like symptoms in our present-day lifestyle. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: External electric fields can regulate the neural network and change the excitability of the in-vivo cerebral cortex. Here, to prove the effect of alternating electric fields on the synaptic plasticity of ex-vivo tissues, the regular changes in the synaptic structure under alternating electric fields were studied. Methods: This study applied alternating electric fields with a peak voltage of 20 V and frequencies of 5, 20, 50, and 80 Hz to the porcine cerebral cortex. Relying on transmission electron microscopy (TEM), the ultrastructure of synapses was observed, and the curvature radius of post-synaptic density (PSD) and the synaptic gap distance was quantified. Results: The results indicated that under alternating electric fields, the average synaptic curvature of the PSD decreased by 30–59% with increasing frequency, and the average synaptic gap distance became narrower. Conclusion: In ex-vivo brain tissue, synaptic plasticity can be regulated by alternating electric fields of different frequencies. This study can provide reference data for the storage and regulation of ex-vivo organs, as well as comparable data for in-vivo studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Alzheimer's disease is the most prevalent form of dementia and is associated with multiple alterations in biological processes. The most profound changes consist of the formation of two types of protein aggregations, called β-amyloid plaques and neurofibrillary tangles of tau proteins. Different biologically relevant metals are believed to play a role during the development of Alzheimer's disease, including copper. In Alzheimer's disease, copper has been reported to interact with β-amyloid plaques and neurofibrillary tangles, while in addition its homeostasis and metabolism are known to be affected. Therefore, Cu was investigated in a murine model mimicking Alzheimer's disease. These mice were genetically manipulated, resulting in the presence of typical Alzheimer's disease symptoms. By making use of two inductively coupled plasma-mass spectrometry (ICP-MS) based analysis techniques, the Cu concentration and the ratio between the natural 65Cu and 63Cu isotopes (65Cu/63Cu) were determined in blood plasma and four different brain regions—brain stem, cerebellum, cortex, and hippocampus—of young and aged Alzheimer's mice and age-matched healthy controls. The Cu concentration in blood plasma was significantly altered in response to both age- and Alzheimer's-related effects, whereas the blood plasma Cu isotope ratio was affected in the Alzheimer's-affected mice only. Both the brain stem and cerebellum showed changes in Cu concentration and 65Cu/63Cu isotope ratio as a result of ageing and the development of Alzheimer's disease. Finally, a correlation was observed between the 65Cu/63Cu isotope ratio in the cerebellum and blood plasma. Determination of Cu concentration and isotope ratio is therefore a relevant tool to unravel the role of Cu in ageing and Alzheimer's disease. Alzheimer's' disease (AD) is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary tangles of tau protein in the brain. Aβ plaques are formed by the cleavage of the β-amyloid precursor protein (APP). In addition to protein aggregations, the metabolism of the essential mineral element Cu is also altered during the pathogenesis of AD. The concentration and the natural isotopic composition of Cu were investigated in blood plasma and multiple brain regions (brain stem, cerebellum, cortex, and hippocampus) of young (3–4 weeks) and aged (27–30 weeks) APPNL-G-F knock-in mice and wild-type controls to assess potential alterations associated with ageing and AD. Tandem inductively coupled plasma-mass spectrometry (ICP-MS/MS) was used for elemental analysis and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for high-precision isotopic analysis. The blood plasma Cu concentration was significantly altered in response to both age- and AD-related effects, whereas the blood plasma Cu isotope ratio was only affected by the development of AD. Changes in the Cu isotopic signature of the cerebellum were significantly correlated with the changes observed in blood plasma. The brain stem showed a significant increase in Cu concentration for both young and aged AD transgenic mice compared with healthy controls, whereas the Cu isotopic signature became lighter as a result of age-related changes. In this work, ICP-MS/MS and MC-ICP-MS provided relevant and complementary information on the potential role of Cu in ageing and AD. [ABSTRACT FROM AUTHOR]

Background and purpose: Huntington’s disease (HD) is a neurodegenerative disease characterized by neuronal death in the striatum. Asiatic acid is an active component of Shorea robusta (Dipterocarpaceae) plants with neuroprotective activity and is considered an acceptable therapeutic candidate for different neurodegenerative diseases. In the present study, the beneficial pharmacological action of Shorea robusta resin extract (SRRE) was assessed in 3-nitropropionic acid (3-NP)-induced HD in rats. Experimental approach: The neuroprotective effect of SRRE (285.7 and 666.7 mg/kg, p.o., 14 days) was studied in 3-NP (10 mg/kg)-induced rats by measuring body weight, behavioral parameters including neurological scoring, motor coordination, spatial memory, and depression-like behavior, neuro-biochemical parameters (gamma-aminobutyric acid and acetylcholinesterase), and oxidative stress parameter in the brain. Histopathology of the rat’s brain was also studied. Findings/Results: SRRE treatment (285.7 mg/kg and 666.7 mg/kg) substantially restored body weight, motor coordination, and mitochondrial enzyme complex I function and improved memory impairment as compared to 3-NP-treated rats. Furthermore, SRRE treatment significantly restored the antioxidant enzyme activity in brain tissue and ameliorated the histopathological changes induced by 3-NP. Conclusion and implications: The neuroprotective effect of SRRE on 3-NP-induced HD in rats was mediated by a reduction in oxidative stress which may favor the usefulness of Shorea robusta in HD.

Alzheimer's Disease (AD) is an irreversible neurodegenerative disease clinically characterized by the presence of β-amyloid plaques and tau deposits in various regions of the brain. However, the underlying factors that contribute to the development of AD remain unclear. Recently, the fusiform gyrus has been identified as a critical brain region associated with mild cognitive impairment, which may increase the risk of AD development. In our study, we performed gene co-expression and differential co-expression network analyses, as well as gene-expression-based prediction, using RNA-seq transcriptome data from post-mortem fusiform gyrus tissue samples collected from both cognitively healthy individuals and those with AD. We accessed differential co-expression networks in large cohorts such as ROSMAP, MSBB, and Mayo, and conducted over-representation analyses of gene pathways and gene ontology. Our results comprise four exclusive gene hubs in co-expression modules of Alzheimer's Disease, including FNDC3A, MED23, NRIP1, and PKN2. Further, we identified three genes with differential co-expressed links, namely FAM153B, CYP2C8, and CKMT1B. The differential co-expressed network showed moderate predictive performance for AD, with an area under the curve ranging from 0.71 to 0.76 (+/- 0.07). The over-representation analysis identified enrichment for Toll-Like Receptors Cascades and signaling pathways, such as G protein events, PIP2 hydrolysis and EPH-Epherin mechanism, in the fusiform gyrus. In conclusion, our findings shed new light on the molecular pathophysiology of AD by identifying new genes and biological pathways involved, emphasizing the crucial role of gene regulatory networks in the fusiform gyrus. [ABSTRACT FROM AUTHOR]