Changes In Nervous System Research Articles

The Effect of Audible Joint Manipulation Sounds in the Upper Cervical Spine on Brain Wave and Autonomic Nervous System Activity

Background: High-velocity, low-amplitude (HVLA) manipulation is a common manual therapy technique used for treating pain and musculoskeletal dysfunction. An audible manipulation sound is commonly experienced by patients who undergo HVLA manipulation; however, there is little known about the effects and clinical relevance of the audible manipulation sound on cortical output and the autonomic nervous system. This study aimed to identify the immediate impact of the audible manipulation sound on brainwave activity and pupil diameter in asymptomatic subjects following an HVLA cervical manipulation. Methods: 40 subjects completed this quasi-experimental repeated measure study design. Subjects were connected to electroencephalography and pupillometry simultaneously, and an HVLA cervical distraction manipulation was performed. The testing environment was controlled to optimize brainwave and pupillometry data acquisition. Pre-manipulation, immediately after manipulation, and post-manipulation data were collected. The presence of an audible manipulation sound was noted. Results: Twenty subjects experienced an audible manipulation sound. Brainwave activity changes were significant (p < 0.05) in both the audible manipulation sound and non-manipulation sound groups. Pupil diameter changes (p < 0.05) occurred in both eyes of the non-manipulation sound group and in the left eye of the audible-manipulation sound group. Brainwave activity patterns were similar in both groups. Conclusions: The presence of an audible manipulation sound is not required to produce central nervous system changes following an HVLA cervical manipulation; however, the audible manipulation sound does prolong the effects of brainwave activity, indicating a prolonged relaxation effect.

Brain and brain blood vessels histological description in autopsies of fetuses/neonates born to mothers with hypertension during pregnancy. A case–control study

Children born to women with hypertension during pregnancy have a two to threefold increased risk of developing cognitive disorders compared to children born to women without hypertension. However, structural changes in the central nervous system of these children remain poorly understood. We aim to compare the brain histological findings from autopsies of neonates and fetuses born to women with and without hypertension during pregnancy. This retrospective case-control study includes brain histological samples from autopsies of neonates and fetuses born to women with (n=22) and without (n=15) hypertension during pregnancy, obtained from biobanks associated with the University Hospital San Ignacio (HUSI), Bogotá, Colombia, between 2007 and 2022. Hypertension during pregnancy was diagnosed following American College of Obstetricians and Gynecologists (ACOG) guidelines. Matched criteria included similar maternal pre-pregnancy morbidity, gestational ages at delivery, fetal sex, and availability of similar histological samples of fetal/neonatal brains. Clinical data were recorded, and two diagnosed-blinded pathologists analyzed all slides. Ninety-three percent (14/15) of fetuses/neonates born to women with hypertension during pregnancy were born after preeclamptic pregnancies. Histological findings were described for the frontotemporal cortex (97%, 36/37) and meninges (81%, 30/37). Fetuses/neonates born to women with hypertension during pregnancy were smaller (p=0.030), had a lower gestational age at death (p=0.047), and were more frequently stillborn. Autopsy records revealed higher maternal vascular malperfusion in women with hypertension during pregnancy (p<0.0001). Subarachnoid hemorrhage was more common in fetuses/neonates born to women with hypertension during pregnancy (p=0.036). Other frequent findings included neuropil edema, congested meninges, hypoxic-ischemic encephalopathy, subdural hematoma, venous sinus thrombosis, hemoventricle, and necrotic foci. However, no significant endothelial or vascular wall changes were noted. "Prominent and congested" capillaries were observed only in fetuses/neonates born to women without hypertension. The findings suggest increased cerebrovascular vulnerability in fetuses and neonates exposed to maternal hypertension during pregnancy, with a higher incidence of subarachnoid hemorrhage. While no vascular wall changes were identified, fewer brain capillary alterations were noted in those born to women with hypertension during pregnancy. Fondecyt 1200250,1240295.

Epidermal Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons.

Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits. Our study reveals that decreased collagen expression, a common age-related phenomenon across species, triggers this process. Specifically, loss-of-function in dpy-5 or col-120, genes encoding cuticular collagens secreted to the epidermal apical surface, induces early-onset excessive dendritic branching and proprioceptive deficits. Adulthood-specific overexpression of dpy-5 or col-120 mitigates excessive branching in aged animals without extending lifespan, highlighting their specific roles in promoting neuronal health span. Notably, collagen reduction specifically drives excessive branching in select sensory neuron subclasses but does not contribute to PVD dendritic beading, another aging-associated neurodegenerative phenotype associated with distinct mechanosensitive dysfunction. Lastly, we identify that rig-3, an immunoglobulin superfamily member expressed in interneurons, acts upstream of collagen genes to maintain PVD dendritic homeostasis during aging, with collagen's regulatory role requiring daf-16/FOXO. These findings reveal that age-related collagen reduction cues neuronal aging independently of collagen's traditional structural support function, possibly involving bi-directional communication processes between neurons and non-neuronal cells. Our study also offers new insights into understanding selective neuron vulnerability in aging, emphasizing the importance of multi-tissue strategies to address the complexities of neuronal aging.

Retinal Microstructural and Microvascular Changes in Alzheimer Disease: A Review.

"The eyes are a window to the brain," prompting the investigation of whether retinal biomarkers can indicate Alzheimer disease (AD) and cognitive impairment. AD is a neurodegenerative condition with a lengthy preclinical phase where pathologic changes in the central nervous system (CNS) occur before clinical symptoms. Mild cognitive impairment (MCI) often precedes AD. As part of the CNS, the retina exhibits similar pathologic changes related to AD as those seen in the brains of patients with MCI. Noninvasive imaging technologies such as optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allow high-resolution visualization of the retina, providing an opportunity to screen and monitor AD noninvasively. In this review, we summarize the relationship between AD and retinal pathology detected by OCT and OCTA. The most common findings in patients with AD include peripapillary retinal nerve fiber layer thinning, decreased macular thickness, an enlarged foveal avascular zone, and decreased vascular densities in the superficial and deep capillary plexuses. These retinal changes correlate with magnetic resonance imaging (MRI) findings of cerebral atrophy, positron emission tomography (PET) findings of increased amyloid load, and neuropsychological testing results suggesting cognitive dysfunction. We conclude that retinal microstructural and microvascular abnormalities may serve as biomarkers for the early detection and clinical monitoring of AD and as tools for evaluating potential treatment effects. Future studies should focus on standardizing protocols for in vivo ophthalmic imaging to measure retinal pathology in AD and MCI.

Comparative transcriptomics suggests a highly species-specific nature of the phenotypic plasticity associated with the outbreaks of the two main pest locusts

BackgroundLocust outbreaks cause devastation and provide material for fundamental research. They associate with a case of phenotypic plasticity whereby the shift between the two extremes of the polyphenism (i.e., gregarious phase versus solitarious phase) affects behaviour as well as most aspects of the locusts’ biology. The phenotypic changes imply changes in gene expression, the changes in behaviour characterize the locusts’ phase change, and the changes in the Central Nervous System (CNS) control the changes in behaviour. Thus, understanding and tackling the phenomenon requires studying the gene expression changes that the locusts’ CNS undergoes between phases. The genes that change expression the same way in different locusts would be ancestrally relevant for the phenomenon in general and some of those that change expression in a species-specific way would be relevant for the phenomenon in species-specific way.MethodsHere, we use available raw sequencing reads to build transcriptomes and to compare the gene expression changes that the CNS of the two main pest locusts (Schistocerca gregaria and Locusta migratoria) undergo when they turn gregarious. The differentially expressed genes resulting from this comparative study were compared with the content of the L. migratoria core transcriptional phase signature genes database. Our aim is to find out about the species-specificity of the phenomenon, and to highlight the genes that respond in the same way in both species.ResultsThe locust phase change phenomenon seems highly species-specific, very likely due to the inter-specific differences in the material used, and in the biology and life conditions of the different locust species. Research on locust outbreaks, gregariousness and swarming would therefore benefit from considering each locust species apart, and caution is needed when extrapolating results between species—as no species seems representative of all locust species. Still, the 109 genes and 39 non-annotated sequences that we found to change expression level the same way in the two main pest locusts, especially those previously reported as core transcriptional phase signature genes in L. migratoria’s CNS-related tissues (10 and 1, respectively), provide material for functional testing in search for important genes to better understand, or to fight against locust outbreaks in a non-species-specific way. The large set of genes that respond in a species-specific way provide material for comparing, understanding and tackling the locust’s phase change phenomenon in a species-specific way. The still uncharacterized transcripts that change expression either in a species-specific or the same way between the two species studied here provide material for gene discovery. Functional testing and confirmation are needed in all cases.

Assessment of neurotoxicity of gadolinium nanocomposite

Introduction. A promising area of nanotoxicology is the study of the effects of gadolinium nanoparticles on a living organism, which will allow achieving high image contrast when performing MRI with a significantly smaller amount of the injected substance. This is possible using high-molecular compounds, for example, arabinogalactan of Siberian larch, which has a stabilizing effect for nanoparticles. Materials and methods. Experimental studies were performed on ninety six mongrel white male rats weighing 180–240 g, divided into 3 groups (one control and two experimental). A water-based solution was used as the exposed substance, which included gadolinium nanoparticles, as well as a nanostabilizing matrix – the natural polysaccharide arabinogalactan. The solution was administered orally for 10 days in two doses – 500 and 5000 mcg of gadolinium per 1 kg of animal body weight. After the introduction, some of the animals were withdrawn from the experiment and made up the early examination period, the remaining part of the animals were left to survive for 6 months and made up the long-term examination period, and subsequently were also withdrawn from the experiment. The work used a set of studies aimed at determining neurotoxicity – the “Open Field” test, EEG examination, morphological and morphometric methods. Results. The structural and functional features of the effect of gadolinium nanocomposite on the central nervous system were expressed in an increase in the number of degeneratively altered neurons when administered a solution at a dose of 500 mcg of gadolinium per 1 kg of animal body weight in the early period of examination, while indices reflecting approximate research activity, behaviour and EEG indices, compared with the control, did not changed. Limitations. When studying the effects of gadolinium nanoparticles encapsulated in the polysaccharide arabinogalactan on 96 outbred male rats, which is sufficient to use a set of methods to determine the functional state of the central nervous system and structural changes in nervous tissue. Conclusion. Thus, the subacute effect of gadolinium nanoparticles encapsulated in the arabinogalactan matrix causes structural changes in the nervous tissue, while functional changes in the central nervous system were not observed.

The Role of Phytochemicals in Managing Neuropathic Pain: How Much Progress Have We Made?

Neuropathic pain is a complex and debilitating condition resulting from nerve damage, characterized by sensations such as burning, tingling, and shooting pain. It is often associated with conditions such as multiple sclerosis (MS), Guillain-Barré syndrome (GBS), and diabetic polyneuropathy. Conventional pain therapies frequently provide limited relief and are accompanied by significant side effects, emphasizing the need to explore alternative treatment options. Phytochemicals, which are bioactive compounds derived from plants, have gained attention for their potential in neuropathic pain management due to their diverse pharmacological properties, including anti-inflammatory, antioxidant, and neuroprotective effects. This review evaluates the mechanisms by which specific phytochemicals, such as curcumin, resveratrol, and capsaicin, influence neuropathic pain pathways, particularly their role in modulating inflammatory processes, reducing oxidative stress, and interacting with ion channels and signaling pathways. While curcumin and resveratrol are primarily considered dietary supplements, their roles in managing neuropathic pain require further clinical investigation to establish their efficacy and safety. In contrast, capsaicin is an active ingredient derived from chili peppers that has been developed into approved topical treatments widely used for managing neuropathic and musculoskeletal pain. However, not all phytochemicals have demonstrated consistent efficacy in managing neuropathic pain, and their effects can vary depending on the compound and the specific condition. The pathophysiology of neuropathic pain, involving maladaptive changes in the somatosensory nervous system, peripheral and central sensitization, and glial cell activation, is also outlined. Overall, this review emphasizes the need for continued high-quality clinical studies to fully establish the therapeutic potential of phytochemicals in neuropathic pain management.

Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.

Neuropathic pain (NP) is an ineffectively treated, debilitating chronic pain disorder that is associated with maladaptive changes in the central nervous system, particularly in the spinal cord. Murine models of NP looking at the mechanisms underlying these changes suggest an important role of microglia, the resident immune cells of the central nervous system, in various stages of disease progression. However, given the number of different NP models and the resource limitations that come with tracking longitudinal changes in NP animals, many studies fail to truly recapitulate the patterns that exist between pain conditions and temporal microglial changes. This review integrates how NP studies are being carried out in murine models and how microglia changes over time can affect pain behavior in order to inform better study design and highlight knowledge gaps in the field. 258 peer-reviewed, primary source articles looking at spinal microglia in murine models of NP were selected using Covidence. Trends in the type of mice, statistical tests, pain models, interventions, microglial markers and temporal pain behavior and microglia changes were recorded and analyzed. Studies were primarily conducted in inbred, young adult, male mice having peripheral nerve injury which highlights the lack of generalizability in the data currently being collected. Changes in microglia and pain behavior, which were both increased, were tested most commonly up to 2 weeks after pain initiation despite aberrant microglia activity also being recorded at later time points in NP conditions. Studies using treatments that decrease microglia show decreased pain behavior primarily at the 1- and 2-week time point with many studies not recording pain behavior despite the involvement of spinal microglia dysfunction in their development. These results show the need for not only studying spinal microglia dynamics in a variety of NP conditions at longer time points but also for better clinically relevant study design considerations.

The neurological damage caused by enterovirus 71 infection is associated with hsa_circ_0069335/miR-29b/PMP22 pathway.

Enterovirus 71 (EV71) infection is usually accompanied by neurological damage, which is the leading cause of death in children with hand-foot-mouth disease. In this study, we demonstrated that EV71 infection can cause pathological damage in the nervous system, such as neuronal vacuolar degeneration, shrinkage of some neurons, edema of brain tissues in the hippocampus, and a decreased number of Nissl bodies in the infarction area. Also, EV71 infection caused apparent structural damage to Schwann cells, including a decreased number of cytoplasmic organelles and severe damage of rough endoplasmic reticulum and mitochondria. However, the pathological damage was alleviated with the decrease of EV71 viral load. The cell experiment in vitro showed that EV71 infection significantly reduced ATP levels and promoted Schwann cell apoptosis, thus inhibiting cell growth. The extended infection time and the decreased viral load resulted in the gradual improvement of cell growth status. Meanwhile, EV71 inhibited the expression of miR-29b and promoted the expression of PMP22 in a time-dependent manner at both mRNA and protein levels, with the most significant change at 36 h of infection. Subsequently, the expression of miR-29b and PMP22 was gradually restored with the reduction of EV71 viral load. In addition, EV71 regulated the expression of hsa_circ_0069335, which could bind and co-localize with miR-29b. Therefore, EV71 infection can cause significant damage to the nervous system and may be related to hsa_circ_0069335/miR-29b/PMP22 pathway. The present study provides a new therapeutic target for neurological damage induced by EV71 infection.IMPORTANCEEV71 can cause severe neurological damage and even death, but the mechanism remains unclear. In this study, we exhibited the pathological changes of nervous system in EV71 infection and revealed that the damage degree was consistent with the EV71 viral load. From the molecular perspective, EV71 infection up-regulated the PMP22 expression in Schwann cells, which is accompanied by apparent structural damage of Schwann cells and myelin sheaths. Furthermore, EV71 promoted the expression of PMP22 and inhibited the expression of miR-29b in a time-dependent manner, with the most significant change at 36 h of infection. Otherwise, the hsa_circ_0069335, which binds and co-localizes with miR-29b, was also regulated by EV71 infection. The hsa_circ_0069335/miR-29b/PMP22 axis may be a potential molecular mechanism involved in EV71 infection-induced fatal neuronal damage. Drug development targeting this pathway may bring clinical improvement of EV71-infected patients.

Multi-domain analysis of ultra-short-term HRV for breathing pattern classification in wearable health devices

This research paper introduces an innovative approach to classify heart rate variability (HRV) time series into paced and spontaneous breathing patterns to reflect changes in the autonomic nervous system. This type of classification is beneficial in wearable devices for stress/relaxation level detection and in deciding therapeutic interventions. The “Multi-Domain Approach” methodology integrates three different techniques: standard HRV features, fuzzy recurrence plot (FRP)-based FRP_GLCM, and empirical mode decomposition-based IMF_FRP_GLCM. The study concentrates on analyzing HRV time series within shorter data segments, aligning with the requirements of contemporary wearable health devices and biofeedback systems. HRV data collected during spontaneous and slow-paced breathing were analyzed across data segments of 5, 4, 3, 2, and 1 min, incorporating feature selection and reduction methods. Results demonstrated that standard HRV features yielded optimal performance for 5-min segments, achieving an average accuracy of 90%. Interestingly, IMF_FRP features achieved comparable accuracy even for 1-min segments. As segment duration decreased, standard HRV feature accuracy declined while IMF_FRP accuracy stayed intact, eventually matching 5-min segment accuracy levels. The study underscores the surging demand for shorter data segment HRV analysis, driven by advancements in wearable smart watches technology and mobile applications for monitoring health and managing stress.

Advancing prediction of age-related vascular cognitive impairment based on peripheral and retinal vascular health in a pilot study: a novel comprehensive assessment developed for a prospective workplace-based cohort (The Semmelweis Study).

With a growing elderly population in the European Union, age-related diseases associated with unhealthy aging pose increasing public health challenges, including a loss of independence and heightened societal burdens. The Semmelweis Study, a prospective occupational cohort study in Hungary, seeks to identify determinants of unhealthy aging, focusing on the complex relationship between lifestyle, environmental, occupational factors, and the development of chronic age-associated diseases, including age-related vascular cognitive impairment (VCI). The primary objective of this pilot study was to establish a robust, high-throughput assessment methodology to comprehensively evaluate both peripheral and cerebrovascular health to provide a solid foundation for the forthcoming Semmelweis Study framework. The study involved 49 participants aged 23 to 87years, and it assessed multi-domain cognitive performance through an automated battery of tests (CANTAB). Vascular health was comprehensively evaluated using laser speckle contrast imaging (LSCI), flow-mediated dilation (FMD), static and dynamic retinal vessel analysis (SVA, DVA), and measurements of vascular stiffness. The retinal microvasculature, which closely mirrors the cerebral circulation in anatomy, physiology, and pathophysiology, provided a unique window for examination. Optical imaging through SVA and DVA enables the identification of structural and functional changes in the central nervous system's microcirculation, which are highly relevant to the pathogenesis of VCI. Subsequently, the collected measures were integrated into vascular health indices using principal component analysis (PCA) and the relationship to the age and cognitive status of study participants was explored. These comprehensive vascular health indices demonstrated a correlation not only with age but also with cognitive performance. This methodology holds promise for providing novel insights into the intricate interplay between vascular and cognitive health within the context of the Semmelweis Study.

Effect of Listening Music on Nulliparous Singleton Pregnancies Who Underwent Induction of Labor: A Randomized Clinical Trial.

A recent randomized clinical trial (RCT) showed that listening to music reduces the pain level and anxiety levels in women with spontaneous labor at term. The effect on pregnant women undergoing induction of labor is still unclear.This study aimed to test the hypothesis that in nulliparous women with singleton pregnancies, undergoing induction of labor at term, listening to music would reduce the pain level during labor. Parallel group, non-blinded, RCT conducted at a single center in Italy. Nulliparous women with singleton pregnancies and vertex presentation, admitted for induction of labor with either oral or vaginal prostaglandins, between 370/7 and 420/7 weeks, were randomized in a 1:1 ratio to receive music during induction of labor or no music during induction. The endpoints of the trials were the pain level during induction, and in the active phase of labor, recorded using the visual analog scale for pain, ranging from 0 (no pain) to 10 (unbearable pain). The effect of music use on each outcome was quantified as the mean difference (MD) with a 95% confidence interval (CI). During the study period, 30 women agreed to take part in the study, underwent randomization, and were enrolled and followed up. Fifteen women were randomized in the music group and 15 in the control group. No patients were lost to follow-up for the primary outcome. Pain level during the induction procedure was 8.8 ± 0.9 in the music group, and 9.8 ± 0.3 in the control group (MD -2.60 points, 95% CI -3.94 to -1.26; p < 0.01). Music during labor and delivery was also associated with decreased anxiety during the induction procedure (MD -3.80 points, 95% CI -5.53 to -2.07; p < 0.01). In nulliparous women, listening to music during the induction of labor reduces pain and anxiety levels. · Music listening has a modulatory effect on the human stress response.. · Music listening may generate beneficial changes in the autonomic nervous system and the HPA axis activity that should be conducive to the stress recovery process.. · Listening to music during induction of labor resulted in a significant lower pain..

Formulation-dependent differences in paclitaxel distribution to anatomical sites relevant to chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event observed in patients receiving paclitaxel, associated with initial pathological changes in the peripheral nervous system, i.e., distal nerves and dorsal root ganglia (DRG). The prevalence of CIPN in patients receiving paclitaxel formulated i) in polyethylated castor oil with ethanol (CreEL-PTX), ii) as albumin-bound (nab-PTX), and iii) in XR17 micelles (micellar-PTX), is unexpectedly varying. We hypothesize that the discrepancy in CIPN prevalence could be governed by differences in the extent of paclitaxel distribution across blood-to-tissue barriers at the CIPN-sites, caused by the specific formulation. The recently developed Combinatory Mapping Approach for CIPN was used to determine the unbound tissue-to-plasma concentration ratio Kp,uu,tissue, after a 4-h infusion of 4mg/kg CreEL-PTX, 4mg/kg nab-PTX or 1mg/kg micellar-PTX in male and female Sprague Dawley rats. Kp,uu,tissue was determined in conventional (DRG, sciatic nerve) and non-conventional (brain, spinal cord, skeletal muscle) CIPN-sites. Based on our data, the Cremophor-free paclitaxel formulations were associated with a higher distribution of paclitaxel to CIPN-sites than CreEL-PTX, e.g., Kp,uu,DRG of 0.70 and 0.60 for nab-PTX and micellar-PTX, respectively, in comparison to 0.27 for CreEL-PTX (p < 0.01). In addition, the fraction of unbound paclitaxel in plasma was on average 1.6-fold higher in nab- and micellar PTX arms and equal to 0.061 and 0.065, respectively, compared to 0.039 for the CreEL-PTX treatment arm (p < 0.0001). In the case of similar unbound paclitaxel concentration in the plasma of patients and assumed species-independent extent of paclitaxel transport across the barriers, nab- and micellar-PTX formulations can lead to higher paclitaxel exposure at CIPN-sites in comparison to CreEL-PTX.

IP-10 acts early in CV-A16 infection to induce BBB destruction and promote virus entry into the CNS by increasing TNF-α expression.

The mechanisms underlying pathological changes in the central nervous system (CNS) following Coxsackievirus A16 (CV-A16) infection have not yet been elucidated. IFN-γ-inducible protein-10 (IP-10) is often used as a predictive factor to monitor early virus infection. It has also been reported that IP-10 plays a pivotal role in neuroinflammation. In this study, we aimed to explore the role of IP-10 in the neuropathogenesis of CV-A16 infection. We observed that the level of IP-10, as well as the TLR3-TRIF-TRAF3-TBK1-NF-κB and RIG-I/MDA5-MAVS-TRAFS-TBK1-NF-κB pathways, which are the upstream of IP-10, were significantly elevated during the course of CV-A16 infection. This increase was accompanied by an increase in a series of inflammatory cytokines at different time-points during CV-A16 infection. To determine whether IP-10 influences BBB integrity, we examined junctional complexes. Our results revealed that the expression levels of Claudin5, Occludin, ZO-1 and VE-Cadherin were notably decreased in CV-A16-infected HUVECs, but these indicators were restored in CV-A16-infected HUVECs with Eldelumab treatment. Nevertheless, IP-10 is only a chemokine that primarily traffics CXCR3-positive immune cells to inflammatory sites or promotes the production of inflammatory cytokines. Therefore, the interactions between IP-10 and inflammatory cytokines were evaluated. Our data revealed that IP-10 mediated the production of TNF-α, which was also observed to change the junctional complexes. Moreover, in a suckling mouse model, IP-10 and TNF-α treatments exacerbated clinical symptoms, mortality and pathological changes in the brain of CV-A16-infected mice, but Anti-IP-10 and Anti-TNF-α treatments alleviated these changes. Our data also revealed that IP-10 may be detected early in CV-A16 infection, whereas TNF-α was detected late in CV-A16 infection, and the production of TNF-α was also found to be positively correlated with IP-10. In addition, IP-10 and TNF-α were observed to reduce junctional complexes and enhance virus entry into the CNS. Taken together, this study provides the first evidence that CV-A16 activates the IP-10/TNF-α regulatory axis to cause BBB damage and accelerate the formation of neuroinflammation in infected hosts, which not only provides a new understanding of the neuropathogenesis caused by CV-A16, but also offers a promising target for the development of CV-A16 antiviral drugs.

Heart Rate Variability and Cerebral Autoregulation in Patients with Traumatic Brain Injury with Paroxysmal Sympathetic Hyperactivity Syndrome.

Severe traumatic brain injury (TBI) can lead to transient changes in autonomic nervous system (ANS) functioning and development of paroxysmal sympathetic hyperactivity (PSH) syndrome. Clinical manifestation of ANS disorders may be obscured by therapeutic interventions in TBI. This study aims to analyze ANS metrics and cerebral autoregulation in patients with PSH syndrome to determine their significance in early prognostication. This single-center retrospective study investigated the relationship between changes in ANS metrics, cerebral autoregulation, and PSH syndrome. Arterial blood pressure and intracranial pressure signals were monitored for 5 days post TBI. ANS metrics included time and frequency domain heart rate variability (HRV) metrics. Cerebral autoregulation was assessed using the pressure reactivity index. Sixty-six patients with severe TBI (median age 33 [interquartile range 26-50] years) were analyzed, and PSH was confirmed in nine cases. Impairment of cerebral autoregulation was observed in 67% of patients with PSH and 72% without the syndrome. Patients with PSH had higher HRV in the low-frequency range (LF; 253 ± 178 vs. 176 ± 227 ms2; p = 0.035) and lower heart rates (HRs; 70 ± 7 vs. 78 ± 19 bpm; p = 0.027) compared to those without PSH. A receiver operating characteristic curve analysis indicated that HR (area under the curve(AUC) = 0.73, p = 0.006) and HRV in the LF (AUC = 0.70, p = 0.009) are moderate predictors of PSH. In the multiple logistic regression model for PSH, diffuse axonal trauma (odds ratio(OR) = 10.82, 95% confidence interval(CI) = 1.70-68.98, p = 0.012) and HR (OR =0.91, 95% CI 0.84-0.98, p = 0.021) were significant factors. Elevated HRV in the LF and decreased HR may serve as early predictors of PSH syndrome development, particularly in patients with diffuse axonal trauma. Further research is needed to investigate the utility of the cerebral autoregulation-ANS relationship in PSH prognostication.

Cardiac autonomic changes after stroke

Abstract Introduction There is a highly complex and clinically important relationship between the cardiac and the nervous system, called the heart-brain axis [1]. Therefore, acute brain damage may lead to alterations in cardiac function due to changes in the autonomic nervous system[2,3]. Novel computerised biosignal analysis techniques and advanced biosignal assessment could provide a valuable tool to sensitively analyse cardiac autonomic function (CAF). CAF can be characterized by two complementary digital biomarkers, periodic repolariation dynamics (PRD) and deceleration capacity (DC). The aim of this study was to determine CAF by means of PRD and DC in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and to analyze them according to their relationship with specific cardiac (high-sensitive Troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP)) and stroke (location, type, severity) characteristics. Methoden / Methods Between February 22, 2021, and May 5, 2023, 282 patients after an AIS or TIA were enrolled in the study. During the inpatient stay, all relevant parameters were recorded and stored in a database. To assess CAF, a 30-minute biosignal measurement was performed with a high resolution (1kHz) electrocardiogram (ECG). Cardiac autonomic biomarkers, PRD and DC, were calculated semiautomatically afterwards from patients. Results Fifteen ECGs were excluded due to poor recording quality. Consequently, data from 261 AIS and 21 TIA patients were analyzed. A total of 105 patients (37.2 %) had pathological PRD (≥ 5.75 deg2) and/or DC (≤ 2.5 ms), 78 patients (27.7 %) had pathological PRD, and 57 patients (20.2 %) had pathological DC. The median PRD was 3.13 deg2 and the median DC was 5.30 ms (see Figure). There were no significant differences in the distribution of PRD and DC between male and female patients (PRD p = 0.38, DC p = 0.30), and between AIS and TIA patients (PRD p = 0.13, DC p = 0.66). Patients with middle cerebral artery (MCA) infarction had significantly higher median PRD values (3.56 deg2 [IQR 1.51 - 6.59 ] vs. 2.81 deg2 [IQR 1.15 - 5.99], p = 0.047) and lower median DC values (4.66 ms [IQR 2.65 – 7.76] vs. 6.11 ms [IQR 3.15 – 10.61], p = 0.011) than patients with stroke located in another cerebral regions (see Figure). Patients with pathological PRD or DC had significantly higher hsTnT (13.50 ng/l [IQR 9.7 – 24.1] vs. 11.05 ng/l [ IQR 7.13 – 16.23], p &amp;lt; 0.001) and NT-pro BNP (269.00 ng/l [IQR 117.50 – 687.00] vs. 125.50 ng/l [IQR 57.00 – 288.25], p &amp;lt; 0.001) values. Conclusions The study showed that a considerable proportion, more than one third of all patients, had evidence of cardiac autonomic dysfunction after acute cerebral ischaemia. Of particular interest, PRD was higher and DC was lower in patients with MCA ischaemia, reflecting a potentially higher cardiac risk profile. Cardiac autonomic dysfunction was also associated with increased hsTnT and NT-proBNP levels.

Task-Based Eating and Drinking Interventions in Animal Models: A Narrative Review of Functional Improvements and Neuromuscular Adaptations in Age-Related Dysphagia.

Age-related dysphagia involves sarcopenia and nervous system changes affecting ingestion. The ACT-ING program, a novel task-based occupational therapy intervention, has been developed to improve strength, endurance, and ingestive skills using real-world eating and drinking tasks for older adults with age-related dysphagia. This narrative review evaluates the outcomes and neuromuscular adaptations of task-based eating and drinking interventions in aging animal models to inform potential refinements of the ACT-ING program and interpret results from an ongoing proof-of-concept study. Publications were obtained from PubMed, SCOPUS, CINAHL, and EMBASE, and selected following the PRISMA guideline. Thirteen randomized trials investigated a task-based fluid-licking intervention in rats, combining strength, endurance, and skill training. Results suggested benefits in improving muscle strength, endurance, and swallowing skills in terms of quantity and speed. Although neuromuscular adaptations were less conclusive, the intervention appeared to induce cortical plasticity and increase fatigue-resistant muscle fibers in the involved muscles. While these findings are promising, methodological concerns and potential biases were identified. Therefore, further research is necessary to refine the ACT-ING program, including both clinical studies in humans and preclinical studies in aging animal models that clearly define interventions targeting all aspects of ingestion-related skills within a motor learning and strength training framework.

Comparative assessment of neurotrophic proteins in vibration disease

Introduction. The problem of health impairment due to the impact of physical factors, including vibration disease (VD), retains medical and social relevance due to the significant specific gravity in the structure of occupational morbidity and high prevalence. Under vibration exposure, the acid-base equilibrium, immune status are disturbed, rheological properties and properties of the neurohumoral system, as well as functional indices of the central and peripheral nervous system change. Neurotrophins are known to play an important role in regulating the development and functioning of the central and peripheral nervous systems. In this regard, research is needed to determine in VD patients the levels of neurospecific proteins, which may serve as one of the markers for tracing changes in the nervous system in workers. The aim of the study was to identify the peculiarities of changes in neurospecific proteins (BDNF, S100β, and MBP) in the serum of patients with VD of different genesis. Materials and methods. Serum concentrations of neurotrophic proteins: brain neurotrophic factor – BDNF, S100β protein and myelin basic protein (MBP) were studied by solid-phase enzyme-linked immunoassay. Results. There was an increase in serum BDNF, S100β protein, and MBP concentrations in persons with VD due to combined exposure to local and general vibration, and an increase in MBP was observed in patients with VD due to exposure to local vibration. Limitations. The limitations of this work are small groups of employees. Conclusion. As a result of studies, it can be assumed that in VD due to exposure to combined vibration, changes are observed in the peripheral and central parts of the nervous system, and in VD due to local vibration, disorders seem to be mainly associated with the peripheral nervous system. The general pattern of the revealed disorders in the content of MBP lies in the neurodestructive processes occurring in the nerve fibers in patients with VD, regardless of genesis. Summarizing the above mentioned, the validity of studying the concentration of neurospecific proteins in vibration disease occurring with damaging processes in the nervous tissue should be recognized.

Autonomous nervous system responses to environmental-level exposure to 5G's first deployed band (3.5GHz) in healthy human volunteers.

Following the global progressive deployment of 5G networks, considerable attention has focused on assessing their potential impact on human health. This study aims to investigate autonomous nervous system changes by exploring skin temperature and electrodermal activity (EDA) among 44 healthy young individuals of both sexes during and after exposure to 3.5GHz antenna-emitted signals, with an electrical field intensity ranging from 1 to 2V/m. The study employed a randomized, cross-over design with triple-blinding, encompassing both 'real' and 'sham' exposure sessions, separated by a maximum interval of 1week. Each session comprised baseline, exposure and postexposure phases, resulting in the acquisition of seven runs. Each run initiated with a 150s segment of EDA recordings stimulated by 10 repeated beeps. Subsequently, the collected data underwent continuous decomposition analysis, generating specific indicators assessed alongside standard metrics such as trough-to-peak measurements, global skin conductance and maximum positive peak deflection. Additionally, non-invasive, real-time skin temperature measurements were conducted to evaluate specific anatomical points (hand, head and neck). The study suggests that exposure to 3.5GHz signals may potentially affect head and neck temperature, indicating a slight increase in this parameter. Furthermore, there was a minimal modulation of certain electrodermal metrics after the exposure, suggesting a potentially faster physiological response to auditory stimulation. However, while the results are significant, they remain within the normal physiological range and could be a consequence of an uncontrolled variable. Given the preliminary nature of this pilot study, further research is needed to confirm the effects of 5G exposure.

Intraperitoneal Injection of the Porphyromonas gingivalis Outer Membrane Vesicle (OMV) Stimulated Expressions of Neuroinflammatory Markers and Histopathological Changes in the Brains of Adult Zebrafish.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The bacteria destroy periodontal tissue through virulence factors, which are retained in the bacteria's outer membrane vesicles (OMV). This study aimed to determine the real-time effect of an intraperitoneal injection of P. gingivalis OMV on the production and expression of inflammatory markers and histopathological changes in adult zebrafishes' central nervous systems (CNS). Following the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMVs, and the control group were injected with normal saline at seven different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA, and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 min, while IL-1β and IL-6 were expressed at subsequent 12 h and 24 h time points, respectively. Histopathological changes such as blood coagulation, astrocytosis, edema, spongiosis, and necrosis were observed between the 6hour and 24 h time points. The two apoptotic enzymes, caspases 3 and 9, were not expressed at any point. In summary, the OMV-induced neuroinflammatory responses and histopathological changes in adult zebrafish were time-point dependent. This study will enrich our understanding of the mechanism of P. gingivalis OMVs in neuroinflammation in a zebrafish model, most especially the timing of the expression of inflammatory mediators in relation to observable changes in brain tissues.