Neural Cells Research Articles

Acylhydrazone Derivative A5 Promotes Neurogenesis by Up-Regulating Neurogenesis-Related Genes and Inhibiting Cell-Cycle Progression in Neural Stem/Progenitor Cells

Adult neurogenesis involves the generation of functional neurons from neural progenitor cells, which have the potential to complement and restore damaged neurons and neural circuits. Therefore, the development of drugs that stimulate neurogenesis represents a promising strategy in stem cell therapy and neural regeneration, greatly facilitating the reconstruction of neural circuits in cases of neurodegeneration and brain injury. Our study reveals that compound A5, previously designed and synthesized by our team, exhibits remarkable neuritogenic activities, effectively inducing neurogenesis in neural stem/progenitor cells (NSPCs). Subsequently, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed to further elucidate the underlying molecular mechanisms by which Compound A5 promotes neurogenesis. Notably, comparative transcriptome analysis showed that the up-regulated genes were mainly associated with neurogenesis, and the down-regulated genes were mainly concerned with cell cycle progression. Furthermore, we confirmed that Compound A5 significantly affected the expression of transcription factors related to neurogenesis and cell cycle regulatory proteins. Collectively, these findings identify a new compound with neurogenic activity and may provide insights into drug discovery for neural repair and regeneration.

Umbilical cord blood stem cells: transplantation prospects in neurological practice

Umbilical cord blood has evolved from being considered a mere cellular/tissue waste product after childbirth to a valuable biological material with a wide regenerative potential. Today, hematopoietic cord blood stem cells are used in the same way as bone marrow and mobilised peripheral blood as part of the standard medical treatment for haemoblastoses and hereditary blood diseases. There is an increasing amount of experimental data showing possibility of umbilical cord blood cell fractions using for treatment of non-hematological diseases and, in particular, diseases of the central nervous system. One of the key challenges in cell therapy for central nervous system diseases is the choice of cellular material for neurotransplantation. This is particularly relevant for ischemic and traumatic injuries, as well as neurodegenerative diseases. Stem or mature somatic cells prepared for neurotransplantation should have predictable and reproducible characteristics thataccording therapeutic purposes, exactly: trophic and/or neuroprotective action to increase neurons viability in damaged area; axon growth stimulation and myelination; cell matrix restoration or predictable differentiation direction to replace amount of lost brain or spinal cord cells. The fact that umbilical cord blood contains not only hematopoietic, but also various non-hematopoietic stem cells with a wide regenerative potential has become the basis for active use of these cells for neurotransplantation. The proposed review provides historical information about umbilical cord blood introduction into practical medicine, its cellular composition and clinical applications of stem cells various types for children central nervous system diseases treatment, such as ischemic encephalopathy, stroke, cerebral hemorrhage, cerebral palsy, autism, and in adults — for stroke treatment, spinal cord injury and neurodegenerative diseases.

Designing efficient brain tumor classifier using hybrid EfficientNet-faster R-CNN deep learning model

Abstract Purpose: Brain tumors have historically posed a significant risk to individuals, potentially leading to fatality. However, in contemporary times, they have emerged as one of the most dangerous health issues affecting both children and adults. The effects of this phenomenon result in the unregulated proliferation of brain cells. Within the field of biological image processing, the utilisation of deep learning algorithms offers a distinct and unparalleled experience. The Convolutional Neural Network (CNN) is a pivotal component in brain tumor categorization applications. However, a notable limitation of CNNs is their extensive execution time, primarily attributed to the substantial number of trainable parameters involved. 
Methods: This study proposes a hybrid model for brain tumor classification that combines faster R-CNN and EfficientNet. The objective is to minimise the time required for classification without compromising accuracy. The data collection from Figshare was employed during the model's development.
Results and Conclusion: The hybrid model proposed in this study demonstrates a notable accuracy of 98.96% during the training phase and 99.2% during the testing phase, surpassing the performance of both the EfficientNet model and the Faster R-CNN model when employed individually. The aforementioned findings were derived through a comparative analysis of the Hybrid model, the EfficientNet model, and the Faster R-CNN model.

Are the promnestic effects of neurokinin 3 receptor mediated by hippocampal neurogenesis in a Aβ-induced rat model of Alzheimer's disease?

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p< 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p< 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p< 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis.

Assembling a coculture system to prepare highly pure induced pluripotent stem cell-derived neurons at late maturation stages.

Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes, and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene expression from the early immature stage to late maturation stages. Mature genes associated with neurodevelopment and synaptogenesis are highly enriched in MNs at late stages, demonstrating that these neurons achieve maturation. This study introduces a novel tool for the preparation of highly pure hiPSC-derived neurons, enabling the determination of neurological disease pathogenesis in neurons at late disease onset stages through biochemical approaches, which typically necessitate highly pure neurons. This advancement is particularly significant in modeling age-related neurodegeneration.Significance Statement Achieving survival poses a significant challenge for long-term neural cell cultures. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we established an indirect coculture system using culture inserts that physically separate neurons and astrocytes, thereby facilitating neuronal maturation. Transcriptomic studies revealed the typical neurodevelopmental switch in gene expression from the early immature stage to late maturation stages, indicating the high quality and maturation of neurons prepared with culture inserts. This study introduces a novel tool for the preparation of highly pure hiPSC-derived neurons, enabling the determination of neurological disease pathogenesis in neurons at late disease onset stages through biochemical approaches, which typically necessitate highly pure neurons. This advancement is particularly significant in modeling age-related neurodegeneration.

Application of GWAS summary data and drug-induced gene expression profiles of neural progenitor cells in psychiatric drug prioritization analysis.

Common psychiatric disorders constitute one of the most substantial healthcare burdens worldwide. However, drug development in psychiatry remains hampered partiallydue to the lack of approaches to estimating drugs that can simultaneously modulate the expression of a nontrivial fraction of disease susceptibility genes. We proposed a new drug prioritization strategy under the framework of our previously proposed phenotype-associated tissues estimation approach (DESE) by investigating the drugs' selective perturbation effect on disease susceptibility genes. Based on the genome-wide association study summary data and drug-induced gene expression profiles of neural progenitor cells, we applied this strategy to prioritize candidate drugs for schizophrenia, depression and bipolar I disorder and identified several known therapeutic drugs among the top-ranked drug candidates. Also, our results revealed that the disease susceptibility genes involved in the selective gene perturbation analysis were enriched with many biologically sensible function terms and interacted with known therapeutic drugs. Our results suggested that selective gene perturbation analysis could be a promising starting point to prioritize biologically sensible drug candidates under the "one drug, multiple targets" paradigm for the drug development of common psychiatric disorders.

Editorial: Space and neural cell: the impact of space environment on neurological function and their molecular mechanistic insights

Editorial: Space and neural cell: the impact of space environment on neurological function and their molecular mechanistic insights

Insights into Brominated Flame Retardant Neurotoxicity: Mechanisms of Hippocampal Neural Cell Death and Brain Region-Specific Transcriptomic Shifts in Mice.

Brominated Flame Retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of HBCD exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (TBBPA, current use), hexabromocyclododecane (HBCD, phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All three BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 μM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed BFR exposure increased LC3-II conversion and autophagosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared to the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of change in vesicular trafficking.

Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?

Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?

Gestational bisphenol A exposure alters energy homeostasis and adult hypothalamic neurogenesis in female mice

Regulation of physiological homeostasis, including energy balance, is thought to be modified by low levels of adult neurogenesis in the hypothalamus. Hormones such as oestradiol can influence both embryonic and adult hypothalamic neurogenic programs, demonstrating a sensitivity of hypothalamic neural progenitor cells to endogenous hormones. Previously we showed that gestational exposure to environmental levels of the xenoestrogen bisphenol A (BPA) changed neural progenitor cell behaviors in the embryo; however, we did not examine if these changes were permanent to affect adult neurogenesis. Here we investigated whether adult neuro- and/or gliogenesis were altered in mice prenatally exposed to BPA and placed on a high-fat diet challenge. Gestationally exposed adult female mice on a standard diet gained less weight than non-BPA controls, whereas gestationally exposed BPA females on a high-fat diet gained more weight than controls. Males exposed to gestational BPA showed no differences in weight gain relative to control males. Concomitantly, adult neurogenesis was increased in the VMH, DMH, and PVN of adult female mice exposed to BPA on standard diet, suggesting that disrupted adult neurogenesis might perturb normal energy balance regulation in females. These results add to growing evidence that low-dose BPA exposure in utero causes changes to adult hypothalamic function.

Increased spontaneous activity and progressive suppression of adult neurogenesis in the hippocampus of rat offspring after maternal exposure to imidacloprid

Imidacloprid (IMI) is a widely used neonicotinoid insecticide that poses risks for developmental neurotoxicity in mammals. The present study investigated the effects of maternal exposure to IMI on behaviors and adult neurogenesis in the hippocampal dentate gyrus (DG) of rat offspring. Dams were exposed to IMI via diet (83, 250, or 750 ppm in diet) from gestational day 6 until day 21 post-delivery on weaning, and offspring were maintained until adulthood on postnatal day 77. In the neurogenic niche, 750-ppm IMI decreased numbers of late-stage neural progenitor cells (NPCs) and post-mitotic immature granule cells by suppressing NPC proliferation and ERK1/2–FOS-mediated synaptic plasticity of granule cells on weaning. Suppressed reelin signaling might be responsible for the observed reductions of neurogenesis and synaptic plasticity. In adulthood, IMI at ≥ 250 ppm decreased neural stem cells by suppressing their proliferation and increasing apoptosis, and mature granule cells were reduced due to suppressed NPC differentiation. Behavioral tests revealed increased spontaneous activity in adulthood at 750 ppm. IMI decreased hippocampal acetylcholinesterase activity and Chrnb2 transcript levels in the DG on weaning and in adulthood. IMI increased numbers of astrocytes and M1-type microglia in the DG hilus, and upregulated neuroinflammation and oxidative stress-related genes on weaning. In adulthood, IMI increased malondialdehyde level and number of M1-type microglia, and downregulated neuroinflammation and oxidative stress-related genes. These results suggest that IMI persistently affected cholinergic signaling, induced neuroinflammation and oxidative stress during exposure, and increased sensitivity to oxidative stress after exposure in the hippocampus, causing hyperactivity and progressive suppression of neurogenesis in adulthood. The no-observed-adverse-effect level of IMI for offspring behaviors and hippocampal neurogenesis was determined to be 83 ppm (5.5–14.1 mg/kg body weight/day).

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P=0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P=0.007], serum creatinine [60 μmol/L (IQR 50-70) versus 70 (54-114); P=0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P=0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P=0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P=0.668 and P=0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8%vs. 8.1%, P=0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P=0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory

Impaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer’s disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment.

Isolation methods and characterization of primary rat neurovascular cells

BackgroundThere is significant interest in isolating cells of the blood-brain barrier (BBB) for use in in vitro screening of therapeutics and analyzing cell specific roles in neurovascular pathology. Primary brain cells play an advantageous role in BBB models; however, isolation procedures often do not produce cells at high enough yields for experiments. In addition, although numerous reports provide primary cell isolation methods, the field is lacking in documentation and detail of expected morphological changes that occur throughout culturing and there are minimal troubleshooting resources. Here, we present simplified, robust, and reproducible methodology for isolating astrocytes, pericytes, and endothelial cells, and demonstrate several morphological benchmarks for each cell type throughout the process and culture timeframe. We also analyze common considerations for developing neurovascular cell isolation procedures and recommend solutions for troubleshooting.ResultsThe presented methodology isolated astrocytes, pericytes, and endothelial cells and enabled cell attachment, maturation, and cell viability. We characterized milestones in cell maturation over 12 days in culture, a common timeline for applications of these cell types in BBB models. Phase contrast microscopy was used to show initial cell plating, attachment, and daily growth of isolated cells. Confocal microscopy images were analyzed to determine the identity of cell types and changes to cell morphology. Nuclear staining was also used to show the viability and proliferation of glial cells at four time points. Astrocyte branches became numerous and complex with increased culture time. Microglia, oligodendrocytes, and neurons were present in mixed glial cultures for 12 days, though the percentage of microglia and neurons expectedly decreased after passaging, with microglia demonstrating a less branched morphology.ConclusionsNeurovascular cells can be isolated through our optimized protocols that minimize cell loss and encourage the adhesion and proliferation of isolated cells. By identifying timepoints of viable glia and neurons within an astrocyte-dominant mixed culture, these cells can be used to evaluate drug targeting, uptake studies, and response to pathological stimulus in the neurovascular unit.

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds.

Multimodal imaging analyses of dosed tissue samples can provide more comprehensive insights into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multimodal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging. Imaging mass spectrometry enables direct mapping of pharmaceutical compounds and metabolites, IHC fluorescence imaging can visualize large proteins, and brightfield microscopy imaging provides tissue morphology information. Single-cell resolution images are generally difficult to acquire using imaging mass spectrometry but are readily acquired with IHC fluorescence and brightfield microscopy imaging. Spatial sharpening of mass spectrometry images would thus allow for higher fidelity coregistration with other higher-resolution microscopy images. Imaging mass spectrometry spatial resolution can be predicted to a finer value via a computational image fusion workflow, which models the relationship between the intensity values in the mass spectrometry image and the features of a high-spatial resolution microscopy image. As a proof of concept, our multimodal workflow was applied to brain tissue extracted from a Sprague-Dawley rat dosed with a kratom alkaloid, corynantheidine. Four candidate mathematical models, including linear regression, partial least-squares regression, random forest regression, and two-dimensional convolutional neural network (2-D CNN), were tested. The random forest and 2-D CNN models most accurately predicted the intensity values at each pixel as well as the overall patterns of the mass spectrometry images, while also providing the best spatial resolution enhancements. Herein, image fusion enabled predicted mass spectrometry images of corynantheidine, GABA, and glutamine to approximately 2.5 μm spatial resolutions, a significant improvement compared to the original images acquired at 25 μm spatial resolution. The predicted mass spectrometry images were then coregistered with an H&E image and IHC fluorescence image of the μ-opioid receptor to assess colocalization of corynantheidine with brain cells. Our study also provides insights into the different evaluation parameters to consider when utilizing image fusion for biological applications.

Dynamic path planning of autonomous bulldozers using activity-value-optimised bio-inspired neural networks and adaptive cell decomposition

Autonomous bulldozers encounter critical challenges in dynamic path planning in complex construction environments such as dynamic obstacles and narrow passages. Bio-inspired neural networks (BINN) are commonly employed for real-time path planning in dynamic environments. However, the algorithm is not feasible enough to calculate the positive input of neighbour cells, thus resulting in unreasonable distribution of activity values in the obstacle-dense regions. Additionally, the use of regular grids results in excessive computation. These drawbacks cause the algorithm to plan irrational paths and reduce computational efficiency. This study proposed an activity-value-optimised BINN and adaptive cell decomposition for the dynamic path planning of autonomous bulldozers. First, an adaptive cell decomposition method was proposed to model a highly intricate and constantly evolving environment, resulting in a reduction in the computational workload of the BINN. Second, the calculation of the activity value is optimised by enhancing the shunt equation of the BINN, which considers both obstacles and grid levels. This improvement enabled more reasonable distribution results. The smoothness of dynamic path planning is refined by incorporating the turning radius, which can be more effectively integrated with local path planning. Compared with the original BINN algorithm and other baseline algorithms, a practical large-scale hydropower project application demonstrated that the proposed method can effectively reduce the number of computational iterations, enrich the travel direction, and improve path quality while ensuring dynamic obstacle avoidance.

Stroke rehabilitation milestone, neurological conditions and future therapy

Stroke rehabilitation milestone, neurological conditions and future therapy Martin Schuettler, Chief Technology Officer of CorTec GmbH, walks us through a groundbreaking achievement in the development of future therapies for neurological conditions like stroke. To develop new treatments for neurological conditions, it is crucial to create suitable devices to support groundbreaking studies. Neuromodulation offers the possibility of treating brain network disorders at their root. Particular networks of brain cells are associated with various functions, e.g. cognitive or motoric capabilities.

The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives

Wilson’s disease (WD) is inherited in an autosomal recessive manner and is caused by pathogenic variants of the ATP7B gene, which are responsible for impaired copper transport in the cell, inhibition of copper binding to apoceruloplasmin, and biliary excretion. This leads to the accumulation of copper in the tissues. Copper accumulation in the CNS leads to the neurological and psychiatric symptoms of WD. Abnormalities of copper metabolism in WD are associated with impaired iron metabolism. Both of these elements are redox active and may contribute to neuropathology. It has long been assumed that among parenchymal cells, astrocytes have the greatest impact on copper and iron homeostasis in the brain. Capillary endothelial cells are separated from the neuropil by astrocyte terminal legs, putting astrocytes in an ideal position to regulate the transport of iron and copper to other brain cells and protect them if metals breach the blood–brain barrier. Astrocytes are responsible for, among other things, maintaining extracellular ion homeostasis, modulating synaptic transmission and plasticity, obtaining metabolites, and protecting the brain against oxidative stress and toxins. However, excess copper and/or iron causes an increase in the number of astrocytes and their morphological changes observed in neuropathological studies, as well as a loss of the copper/iron storage function leading to macromolecule peroxidation and neuronal loss through apoptosis, autophagy, or cuproptosis/ferroptosis. The molecular mechanisms explaining the possible role of glia in copper- and iron-induced neurodegeneration in WD are largely understood from studies of neuropathology in Parkinson’s disease and Alzheimer’s disease. Understanding the mechanisms of glial involvement in neuroprotection/neurotoxicity is important for explaining the pathomechanisms of neuronal death in WD and, in the future, perhaps for developing more effective diagnostic/treatment methods.

Assessment of Stroke Patients' Muscle Strength Following a Combination of Mirror Therapy and ROM (Range of Motion) Exercises Based on Self-Care Theory

Background: When blood flow problems kill off some brain cells, the result is a neurological deficiency known as a stroke. There have been 507 reported cases of stroke in East Java, while the overall stroke prevalence in Indonesia has jumped from 7% to 10.9% (Riskesdas, 2020). The researchers at RSI Darus Syifa's Surabaya set out to determine how much of an impact self-care theory-based mirror therapy and range-of-motion exercises had on the muscular strength of stroke patients admitted to the inpatient unit. Methods: A true experimental with a pretest-posttest control group design was utilised in this type of research. One hundred and ten stroke patients made up the study's population. There were a total of 34 participants in this study, with 17 serving as control subjects and 17 as interventionists. Sampling was based on probability sampling using simple random sampling. The Medical Research Council (MRC) scale was utilised by the device to measure muscular strength. Mann-Whitney and the Wilcoxon Signet Rank Test were used to examine the collected data. Results: In the inpatient ward of the Darus Syifa Surabaya Hospital, stroke patients who undergo a combination of mirror therapy and range of motion exercises based on self-care theory show a significant improvement in muscle strength, according to the Mann-Whitney test (p &lt; 0.05). Conclusion: The study found that stroke patients' muscle strength improved with a combination of mirror therapy and range of motion exercises grounded in self-care theory.

Tetrodotoxin-resistant mechanosensitivity and L-type calcium channel-mediated spontaneous calcium activity in enteric neurons.

Gut motility undergoes a switch from myogenic to neurogenic control in late embryonic development. Here, we report on the electrical events that underlie this transition in the enteric nervous system, using the GCaMP6f reporter in neural crest cell derivatives. We found that spontaneous calcium activity is tetrodotoxin (TTX) resistant at stage E11.5, but not at E18.5. Motility at E18.5 was characterized by periodic, alternating high- and low-frequency contractions of the circular smooth muscle; this frequency modulation was inhibited by TTX. Calcium imaging at the neurogenic-motility stages E18.5-P3 showed that CaV1.2-positive neurons exhibited spontaneous calcium activity, which was inhibited by nicardipine and 2-aminoethoxydiphenyl borate (2-APB). Our protocol locally prevented muscle tone relaxation, arguing for a direct effect of nicardipine on enteric neurons, rather than indirectly by its relaxing effect on muscle. We demonstrated that the ENS was mechanosensitive from early stages on (E14.5) and that this behaviour was TTX and 2-APB resistant. We extended our results on L-type channel-dependent spontaneous activity and TTX-resistant mechanosensitivity to the adult colon. Our results shed light on the critical transition from myogenic to neurogenic motility in the developing gut, as well as on the intriguing pathways mediating electro-mechanical sensitivity in the enteric nervous system. HIGHLIGHTS: What is the central question of this study? What are the first neural electric events underlying the transition from myogenic to neurogenic motility in the developing gut, what channels do they depend on, and does the enteric nervous system already exhibit mechanosensitivity? What is the main finding and its importance? ENS calcium activity is sensitive to tetrodotoxin at stage E18.5 but not E11.5. Spontaneous electric activity at fetal and adult stages is crucially dependent on L-type calcium channels and IP3R receptors, and the enteric nervous system exhibits a tetrodotoxin-resistant mechanosensitive response. Abstract figure legend Tetrodotoxin-resistant Ca2+ rise induced by mechanical stimulation in the E18.5 mouse duodenum.