Neural Pathways Research Articles

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

Dissecting the causal role of early inferior frontal activation in reading.

Cognitive models of reading assume that speech production occurs after visual and phonological processing of written words. This traditional view is at odds with more recent magnetoencephalography studies showing that the left posterior inferior frontal cortex (pIFC) classically associated with spoken production responds to print at 100-150 ms after word-onset, almost simultaneously with posterior brain regions for visual and phonological processing. Yet the theoretical significance of this fast neural response remains open to date. We used transcranial magnetic stimulation (TMS) to investigate how the left pIFC contributes to the early stage of reading. In Experiment 1, 23 adult participants (14 females) performed three different tasks about written words (oral reading, semantic judgment and perceptual judgment) while single-pulse TMS was delivered to the left pIFC, fusiform gyrus or supramarginal gyrus at different time points (50 to 200 ms after word-onset). A robust double dissociation was found between tasks and stimulation sites - oral reading, but not other control tasks, was disrupted only when TMS was delivered to pIFC at 100 ms. This task-specific impact of pIFC stimulation was further corroborated in Experiment 2, which revealed another double dissociation between oral reading and picture naming. These results demonstrate that the left pIFC specifically and causally mediates rapid computation of speech motor codes at the earliest stage of reading and suggest that this fast sublexical neural pathway for pronunciation, although seemingly dormant, is fully functioning in literate adults. Our results further suggest that these left-hemisphere systems for reading overall act faster than known previously.Significance Statement Recent neuroimaging data suggest that left posterior inferior frontal cortex, classically associated with spoken production, responds to print simultaneously with left fusiform and supramarginal gyri, each responsible for visual and phonological processing, contrary to traditional serial cascade models of reading. While the region is now known to mediate different aspects of cognitive processing, the functional significance of this fast neural response remains unclear. Using transcranial magnetic stimulation, we show that early inferior frontal activation plays a specific and causal role in speeded oral reading at 100 ms after word-onset. This fast sublexical neural pathway for pronunciation, although seemingly dormant, is fully functioning in literate adults. We also propose that the left-hemisphere reading systems act differently and faster than known previously.

Brain functional connectivity under teleoperation latency: a fNIRS study

IntroductionLong-distance robot teleoperation faces high latencies that pose cognitive challenges to human operators. Latency between command, execution, and feedback in teleoperation can impair performance and affect operators’ mental state. The neural underpinnings of these effects are not well understood.MethodsThis study aims to understand the cognitive impact of latency in teleoperation and the related mitigation methods, using functional Near-Infrared Spectroscopy (fNIRS) to analyze functional connectivity. A human subject experiment (n = 41) of a simulated remote robot manipulation task was performed. Three conditions were tested: no latency, with visual and haptic latency, with visual latency and no haptic latency. fNIRS and performance data were recorded and analyzed.ResultsThe presence of latency in teleoperation significantly increased functional connectivity within and between prefrontal and motor cortexes. Maintaining visual latency while providing real-time haptic feedback reduced the average functional connectivity in all cortical networks and showed a significantly different connectivity ratio within prefrontal and motor cortical networks. The performance results showed the worst performance in the all-delayed condition and best performance in no latency condition, which echoes the neural activity patterns.ConclusionThe study provides neurological evidence that latency in teleoperation increases cognitive load, anxiety, and challenges in motion planning and control. Real-time haptic feedback, however, positively influences neural pathways related to cognition, decision-making, and sensorimotor processes. This research can inform the design of ergonomic teleoperation systems that mitigate the effects of latency.

Bacteriocin Microcin J25's antibacterial infection effects and novel non-microbial regulatory mechanisms: differential regulation of dopaminergic receptors.

The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined. Here, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB. Our studies' findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.

Abstract Su805: Early-Latency Evoked Brain Response Revealed using Novel Filtering Technique

Background: Cardiac arrest (CA) can cause coma in resuscitated patients. Accuracy of prognosis is limited. Presence of brain signals such as somatosensory evoked potential (SSEP) reveals integrity of the thalamocortical pathway, which is necessary for arousal but insufficient to predict positive outcome. The N10 is a SSEP component that diminishes in CA. The N7, which can be obscured by stimulus artifact or other components, is associated with subcortical structures. Phase space area (PSA) quantifies SSEP morphology and is associated with CA recovery. It has been measured at least 5ms after stimulus. Hypothesis: Early SSEP and PSA diminish under anesthesia and during CA but may recover afterwards. Aims: By removing stimulus artifact, we capture early SSEP (N7 and early PSA) to enable improved prognostication. Methods: Six rats received 1.2, 1.8, and 2.5% isoflurane anesthesia for 30min. Two underwent 5 or 7min CA and were observed over 2hr. SSEP was recorded every 2s. An adaptive filter removed the artifact. Peaks were measured near 7 (N7) and 15 (N10) ms post-stimulus. PSA, the area occupied by the phase space curve, was recorded over 0-9ms (“early”) and 0-30ms (“total”). Signal-to-noise ratio (SNR) is the ratio of N10 amplitude to standard deviation of the signal. T tests were used for comparisons between SNR values and between experimental conditions. Results: We identified 4153 N7 peaks with latency (mean±95% C.I.) 8.6±1.3ms in the filtered data, compared to 2464 with latency 8.5±1.4ms in the unfiltered data. SNR was greater in the filtered signal (2.3±1.5) than unfiltered (0.3±0.4). N7 amplitude decreased at the highest anesthesia level; N10 decreased for each level. N7 and N10 decreased during CA and recovered after, although N10 remained below baseline during 2hr recovery. Early PSA was lower under the higher anesthesia levels, while total PSA decreased for each level. PSA decreased during CA and recovered after 5min CA; total PSA recovered to baseline and early PSA exceeded it after 2hr.Early PSA did not recover from 7min CA, while total PSA recovered but remained below baseline. Conclusion: We demonstrate a novel technique to discover an elusive early-latency response, adding detail to a neural pathway involved in arousal. We reduce noise, capture N7 consistently, and measure PSA beginning at 0ms, providing additional diagnostic dimensions responsive to anesthesia and CA. Future study will investigate outcomes in resuscitated patients.

Pyrfume: A window to the world's olfactory data.

Advances in theoretical understanding are frequently unlocked by access to large, diverse experimental datasets. Our understanding of olfactory neuroscience and psychophysics remain years behind the other senses, in part because rich datasets linking olfactory stimuli with their corresponding percepts, behaviors, and neural pathways remain scarce. Here we present a concerted effort to unlock and unify dozens of stimulus-linked olfactory datasets across species and modalities under a unified framework called Pyrfume. We present examples of how researchers might use Pyrfume to conduct novel analyses uncovering new principles, introduce trainees to the field, or construct benchmarks for machine olfaction.

Neural Pathways of Social Cognition: From Systems Neuroscience to Psychosocial Applications

The neural pathways underlying social cognition form the basis of human interaction, encompassing processes such as empathy, theory of mind, and social decision-making. This research explores the intersection of systems neuroscience and psychosocial applications, unraveling the neural circuits that enable individuals to perceive, interpret, and respond to social stimuli. Key brain regions such as the medial prefrontal cortex, temporoparietal junction, and amygdala play pivotal roles in these processes, facilitating complex functions like perspective-taking and emotional resonance. By integrating insights from neuroimaging, behavioral studies, and computational modeling, this study aims to map the mechanisms that govern social cognition and their disruptions in conditions such as autism, schizophrenia, and social anxiety. The research also emphasizes the translation of these findings into psychosocial interventions, including therapeutic strategies and social skills training programs. Understanding the neural underpinnings of social cognition has far-reaching implications for enhancing interpersonal relationships, fostering inclusivity, and addressing the challenges posed by neuropsychiatric disorders.

EPCO-21. ELUCIDATING THE FUNCTIONAL RELEVANCE OF ATRX-DEFICIENCY IN H3.3-G34-MUTANT DIFFUSE HEMISPHERIC GLIOMA

Abstract Diffuse hemispheric gliomas (DHGs) account for 30% of aggressive cerebral tumors in children and young adults, exhibiting abysmal outcomes. Co-existing recurrent mutations in H3.3 histones at residue G34 (H3.3-G34R/V mutation) and concurrent inactivating mutations in TP53 and α-thalassemia/intellectual disability-X-linked gene (ATRX) implicate a coordinated molecular effort to drive oncogenesis. ATRX, a core component of the SWItch/Sucrose Non-Fermentable chromatin remodeling complex, regulates the incorporation of histone H3.3 into chromatin sites across the genome to maintain epigenome integrity. Yet, it is unclear how ATRX loss combines with H3.3-G34R/V mutations to influence cellular phenotype and dysregulate neuro-developmental programs. We propose that ATRX deficiency coordinates with key oncogenic partners by inducing oncogenic transcriptional programs and neuro-developmental pathways in DHGs. To investigate this, we employed CRISPR-editing to model H3.3-G34R followed by ATRX knockdown (ATRX-KD) in a TP53 mutant (TP53-mut) human-induced pluripotent stem cell (h-iPSC) line, developing an isogenic system to map contributions to epigenetic dysfunction made by specific molecular alterations. Upon differentiation of our h-iPSCs to neural stem cells (NSCs), we found unique transcriptional profiles associated with each genetic alteration, with upregulation of forebrain progenitor genes driven by ATRX-loss. Hierarchal clustering of normalized transcript counts revealed gene signatures from each model driving unique functional pathways, with the ATRX-KD and the triple mutant (TP53-mut, ATRX-KD, H3.3-G34R) signatures enriched for neural development pathways. Additionally, both signatures were associated with published transcriptional profiles of G34-mutant DHGs, emphasizing the disease relevance of our models. Further, time-course analysis using cerebral organoids uncovered distinct morphological changes with each alteration, with the triple mutant exhibiting impaired differentiation at later time points. These latter findings suggest that ATRX deficiency transcriptionally influences early neuronal differentiation, effects further refined by H3.3-G34 mutation. To conclude, our innovative models demonstrate the involvement of ATRX in neuro-developmental and differentiation phenotypes, illuminating underlying molecular features of aggressive DHGs.

INNV-28. CONNECTOMICS-GUIDED GLIOMA RESECTION: HOW CHANGES IN STRUCTURAL CONNECTIVITY CORRELATE WITH LANGUAGE FUNCTION

Abstract Postoperative aphasia is a risk inherent to resections of brain masses in language eloquent areas. Neurosurgical strategies to minimize damage of functional language structures include awake craniotomies combined with stimulation mapping and intra-operative speech and language pathology (SLP) testing. Until now, consideration of white matter tracts involved in language processing as measured by diffusion tensor imaging (DTI) has been minimally incorporated into resection planning. In addition, there is limited understanding as to the association between specific tracts and aphasia risk. Quicktome™ by Omniscient Neurotechnology is clinically-oriented connectomics software that uses DTI sequences from MRIs to model connectivity between geographically distinct brain regions. This model can then be integrated with intraoperative navigation to avoid language connections during resection. Here, we investigate how language tract changes affect clinical aphasia. Patients with language-eloquent gliomas with available pre- and post-operative DTI and SLP evaluations were included in this retrospective study. Structural networks were quantified using Quicktome™ and compared using Spearman correlation. Changes in language function were evaluated using the Boston Naming Test and the Western Aphasia Battery. Patients with postoperative auditory verbal deficits showed a moderate correlation in connectivity changes (ρ=0.42), whereas patients with postoperative naming deficits showed a weak correlation (ρ=0.19). The inferior frontal junction, anterior portion (IFJa), and the superior temporal sulcus, ventral posterior portion (STSvp), in the right hemisphere demonstrated the most associated structural connectivity changes. To our knowledge, this is the first study which uses Quicktome™ to directly associate postoperative connectivity with aphasia outcomes. Understanding the interplay between structural connectivity and neurological symptoms can elucidate neural pathways underlying cortical function with the potential to reduce neurosurgical postoperative morbidity.

Mother-Child Closeness and Adolescent Structural Neural Networks: A Prospective Longitudinal Study of Low-Income Families.

Mother-child closeness, a mutually trusting and affectionate bond, is an important factor in shaping positive youth development. However, little is known about the neural pathways through which mother-child closeness are related to brain organization. Utilizing a longitudinal sample primarily from low-income families (N=181; 76% African American youth and 54% female), this study investigated the associations between mother-child closeness at ages 9 and 15 and structural connectivity organization (network integration, robustness, and segregation) at age 15. The assessment of mother-child closeness included perspectives from both mother and child. The results revealed that greater mother-child closeness is linked with increased global efficiency and transitivity, but not modularity. Specifically, both the mother's and child's report of closeness at age 15 predicted network metrics but report at age 9 did not. Our findings suggest that mother-child closeness is associated with neural white matter organization, as adolescents who experienced greater mother-child closeness displayed topological properties indicative of more integrated and robust structural networks.

Functional connectivity in procrastination and emotion regulation

Procrastination, an irrational delay of intended action, leads to numerous adverse effects in many life domains, such as low academic performance, poor mental health, and financial distress. Previous studies have revealed a substantial negative correlation between emotional regulation and procrastination. However, the neural basis for the association between emotion regulation and procrastination remains unclear. Therefore, we employed the voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods to explore the neural substrates underlying how emotion regulation is responsible for procrastination (N = 243). In line with our hypothesis, the results showed a significant negative correlation between emotion regulation ability and procrastination. Additionally, the VBM analysis showed that emotion regulation ability was positively correlated with gray matter (GM) volumes in the right dorsal-lateral prefrontal cortex (dlPFC). The mediation analysis revealed that emotion regulation ability mediated the relationship between the GM volumes of the right dlPFC and procrastination. Furthermore, the RSFC results indicated that right dlPFC-left insula functional connectivity was positively associated with emotion regulation ability. Emotion regulation ability further mediated the relationship between the right dlPFC-left insula functional connectivity and procrastination. The current findings suggest that the neural pathway related to cognitive control over aversive emotion may be responsible for the close relationship between emotion regulation and procrastination, which provides a novel perspective for explaining the tight association between emotion regulation and procrastination.

Dysgraphia and Memory: Insights into the Cognitive Mechanisms, Neural Correlates, and Intervention Strategies.

Studies regarding dysgraphia, an impairment in writing, have been receiving more attention in recent research. Most studies have broadly discussed the multiple cognitive mechanisms involved in writing and its disruption leading to dysgraphia. However, little attention has been paid to the involvement of different memory systems integral to writing and its disruption in individuals with dysgraphia. Orthographic long-term memory and orthographic working memory are the two memory systems predominantly involved in the production of written expressions, and the subsequent interruption of these memory systems often leads to varied deficit profiles of dysgraphia. These disruptions have resulted from damage in the brain caused by neural injuries, neurological disorders, or epigenetic factors. The existing studies did not probe into the nuances of the disruptions of these two memory systems in dysgraphia and associated neural pathways. In order to fill this gap, the review attempts to provide a comprehensive account of dysgraphia and its association with orthographic long-term memory and orthographic working memory by comparing and contrasting their workings and patterns of disruption in the deficit profiles of dysgraphia by probing into the underlying neural correlates. Such a detailed account brings insights into pertinent intervention strategies for improving memory systems and dysgraphia. It also helps identify the limitations of the existing intervention methods like CART, ACT, or Spell-Study-Spell, leading to the proposal of improvised neuro-targeted interventions for dysgraphia.

Transplantation of peripheral nerve tissueoid based on a decellularized optic nerve scaffold to restore rat hindlimb sensory and movement functions

Peripheral nerve injury (PNI) involving the loss of sensory and movement functions is challenging to repair. Although the gold standard of PNI repair is still the use of autologous nerve grafts, the destruction of the donor side is inevitable. In the present study, peripheral nerve tissueoids (PNTs) composed of a Schwann cell (SC)-based neurotrophin-3 (NT-3) delivery system and a decellularized optic nerve (DON) with naturally oriented channels were engineered to investigate the mechanism of PNTs in nerve regeneration. Proteomic analysis and mRNA sequencing revealed that PNTs have the advantage of promoting nerve regeneration by the three mechanisms of chemotaxis, adhesion and intrinsic mobilisation. The results demonstrated that a local NT-3-enriched pool was constructed by laminin γ3 (LAMC3) in PNTs, creating a niche for the colonization of TrkC-positive SCs, attraction of axons to the defect/graft area, and remyelination. In addition, LAMC3 in PNTs can rapidly promote axon adhesion through integrin aVβ6 and can precisely guide long projecting axons to target tissues. Furthermore, the interactions among the NT-3/TrkC, LAMC3/integrin aVβ6 and the scaffold synergistically activate the PI3K-AKT signalling pathway in damaged neurons, further stimulating the intrinsic regenerative drive within the neurons to ultimately achieve the rapid reinnervation and the improvement of sensory and movement functions in the hindlimb.

Propagation effect of the thalamic feed-forward and feed-back inhibition in multi-type coupling models.

Seizure waves of epilepsy can propagate in a coupled thalamocortical model, which typically occurs in malfunctioning neuronal networks. However, it remains unclear whether thalamic feed-forward inhibition (FFI) and feed-back inhibition (FBI), the two most important microcircuits in this network, have propagation effects. In this study, we first investigated the importance of the pyramidal neuronal population-thalamic reticular nucleus and specific relay nucleus-thalamic reticular nucleus pathways in the Taylor model for seizure control as FFI and FBI, respectively. Subsequently, using the FBI as a crucial parameter, we constructed 2- and 3-compartment coupling models and evaluated their impact on seizure propagation in other chambers by varying the degree of coupling strength. Finally, we replicated the above study in a 10-compartment model to ensure the robustness of the findings. We confirmed that FBI is more effective by analyzing the combined effect of FFI and FBI, and the pathology state does advance as the coupling strength is increased. These findings elucidate the roles that these two pathways play in the propagation of epileptic seizures and may offer fresh perspectives on the clinical management of epilepsy.

Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases.

Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

Morphological similarity and white matter structural mapping of new daily persistent headache: a structural connectivity and tract-specific study

BackgroundNew daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH.MethodsThe regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features.ResultsT1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression.ConclusionsOur research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

The eyestalk photophore of Northern krill Meganyctiphanes norvegica (M. Sars) (Euphausiacea) re-investigated: Innervation by specialized ommatidia of the compound eye

Members of the Euphausiacea (“krill”) generate bioluminescence using light organs, the so-called photophores, including one pair associated with the eyestalks, two pairs on the thoracic segments, and four unpaired photophores on the pleon. The photophores generate light via a luciferin–luciferase type of biochemical reaction in light-emitting cells comprised in a photophore compartment called “lantern”. The behavioral significance of bioluminescence in krill is discussed controversially, and possible functions include a defensive function, camouflage by counter-shading, and intra-specific communication. Light production of all krill photophores is controlled by hormonal and neuronal pathways but our knowledge about the nature of these pathways is still rudimentary. Here, we provide a detailed description of the eyestalk photophore's histology in Northern krill Meganyctiphanes norvegica, and used immunohistochemistry combined with confocal laser-scan microscopy to explore this organ's serotonergic innervation. Furthermore, we provide evidence that the photophore is innervated by a distinct photophore nerve that originates from a specialized cluster of ca. 30 highly modified ommatidia at the dorsal rim of the compound eye that are optically isolated from the other ommatidia. Our findings suggest the compound eye – photophore link as a major anatomical axis to adjust the photophore activity.

Ex vivo and miniaturized in vitro models to study microbiota-gut-brain axis.

The microbiota-gut-brain axis involves complex bidirectional communication through neural, immune, and endocrine pathways. Microbial metabolites, such as short-chain fatty acids, influence gut motility and brain function by interacting with gut receptors and modulating hormone release. Additionally, microbial components such as lipopolysaccharides and cytokines can cross the gut epithelium and the blood-brain barrier, impacting immune responses and cognitive function. Ex vivo models, which preserve gut tissue and neural segments, offer insight into localized gut-brain communication by allowing for detailed study of nerve excitability in response to microbial signals, but they are limited in systemic complexity. Miniaturized in vitro models, including organ-on-chip platforms, enable precise control of the cellular environment and simulate complex microbiota-host interactions. These systems allow for the study of microbial metabolites, immune responses, and neuronal activity, providing valuable insights into gut-brain communication. Despite challenges such as replicating long-term biological processes and integrating immune and hormonal systems, advancements in bioengineered platforms are enhancing the physiological relevance of these models, offering new opportunities for understanding the mechanisms of the microbiota-gut-brain axis. This review aims to describe the ex vivo and miniaturized in vitro models which are used to mimic the in vivo conditions and facilitate more precise studies of gut brain communication.

Multifunctional hydrogels loaded with tellurium nanozyme for spinal cord injury repair

Spinal cord injury (SCI) results in severe neurological deficits due to disrupted neural pathways. While the spinal cord possesses limited self-repair capabilities, recent advancements in hydrogel-based therapies have shown promise. Polyphenol-based hydrogels, known for their neuroprotective properties, offer a suitable microenvironment for neural regeneration. In this study, a novel poly(lipoic acid)/poly(dopamine) adhesive hydrogel was developed as a versatile platform for delivering therapeutic agents. This hydrogel was loaded with methylcobalamin, a neurotrophic factor, and tellurium nanoenzymes, potent antioxidants. The nanoenzymes effectively mitigated oxidative stress and inflammation, while methylcobalamin promoted nerve regeneration. The combined therapeutic effects of the nanoenzymatic hydrogel demonstrated significant efficacy in repairing spinal cord injuries, highlighting its potential as a promising strategy for treating this debilitating condition.

Enhancing pediatric comfort: a comprehensive approach to managing molar-incisor hypomineralization with preemptive analgesia and behavioral strategies.

Preemptive analgesia is an important strategy used in pediatric dentistry to intercept pain signals in neural pathways early, thus mitigating the perception of pain and enhancing overall patient comfort. Pedodontists often encounter challenges in conducting the therapy and managing uncooperative patients, when addressing enamel defects of the Molar-incisor hypomineralization (MIH) type. The aim of this study is to demonstrate the impact of preemptive analgesia on optimizing behavioral management and restorative treatment strategies for immature permanent molars exhibiting severe MIH and Treatment need index 4 (TNI), through the effective control of pain. This study comprised 27 cases with MIH level 3 Posteruptive breakdown (PEB), indicating post-eruptive enamel breakdown, with initial hypersensitivity scores exceeding 4 on the Wong-Baker Scale, was conducted over 12 months, between January 2023-January 2024. Data on pediatric patients aged between 5 years and 4 months and 7 years and 1 month with varying degrees of sensitivity in their permanent first molars before the completion of the eruption process were collected. Pain intensity was systematically evaluated at six specific time points: before and after the administration of analgesic medication as well as during restorative treatment using the Wong-Baker scale and data from the Face, Legs, Activity, Cry, Consolability index (FLACC). Statistical analysis for Wong-Baker scores and FLACC index indicated statistical significance (p < 0.05) for Mann-Whitney and Wilcoxon tests, respectively t-test. The comparison of mean scores recorded before and after preemptive analgesia during rotary instrumentation moments for the Wong-Baker index (4 > 0.29) and for the FLACC index (8.47 > 1.71) indicates the positive influence of administering ibuprofen. In conclusion, preemptive analgesia, alongside standardized anesthesia, significantly improved intraoperative pain management and behavioral outcomes.