Nervous Systems Research Articles

Neuropsychological mechanisms of observational learning in human placebo effects.

Scientific evidence indicates that placebo effects are psychoneurobiological events involving the contribution of distinct central nervous systems and peripheral physiological mechanisms that influence pain perception and other symptoms. Placebo effects can occur without formal conditioning and direct prior experience because crucial information can be acquired through observational learning. Observation of benefits in another person results in placebo effects of a magnitude like those induced by directly experiencing an analgesic benefit. Understanding the psychological mechanisms of observationally induced placebo effects is a complex and multifaceted endeavor. While previous reviews have highlighted various frameworks and models to understand these phenomena, the underlying biological mechanisms have been overlooked. We summarize critically current understanding of its behavioral and neural mechanisms. Understanding the neural mechanisms of hypoalgesia driven by observation can serve as a foundation for future development of novel theoretical and methodological approaches and ultimately, applications.

Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture.Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling.Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE.Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Beta-Cyfluthrin-Induced Hepatic Alterations in Zebrafish: Enzymatic Profiles and Oxidative Stress Responses

Beta-Cyfluthrin is a widely used pesticide belonging to class of synthetic pyrethroids which affects the central and peripheral nervous systems. The current study investigates the impact of beta-Cyfluthrin on the biochemical parameters of liver of zebrafish (Danio sp.). Adult zebrafish were exposed to concentrations of 0.25, 0.5, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin for acute (96 hours) and chronic (21 days) exposure periods respectively (n=20). It was observed that exposure to beta-Cyfluthrin led to variations in biochemical markers in both acute and chronic exposure groups. Liver function tests revealed significant elevated activity of alanine transaminase (ALT) and aspartate transaminase (AST) at exposure concentrations of 2.0 and 4.0 µg/L of beta-Cyfluthrin in both acute and chronic groups, while acid phosphatase (ACP) and alkaline phosphatase (ALP) activity decreased significantly at concentrations of 1.0, 2.0 and 4.0 µg/L in the chronic group. Lipid peroxidation exhibited a concentration and time-dependent increase with significant difference at 1.0, 2.0 and 4.0 µg/L in both acute and chronic groups, while superoxide dismutase (SOD) and peroxidase (PER) levels declined significantly in both acute and chronic exposure groups at exposure concentrations of 1.0, 2.0 and 4.0 µg/L for SOD and 2.0 and 4.0 µg/L for PER. Catalase (CAT) initially increased significantly in acute groups of 1.0, 2.0 and 4.0 µg/L but decreased in chronic ones. Glutathione S-transferase (GST) levels exhibited a significant increase at lower concentrations of 0.25 µg/L but a decrease at higher concentrations, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin. The level of significance were considered at p<0.05 and p<0.01. This research suggests that exposure to beta-Cyfluthrin leads to hepatic damage in adult zebrafish. This indicates a potential risk to non-target aquatic fauna, through runoff where beta-Cyfluthrin is used as an agricultural pesticide.

Heart rate variability as a preictal marker for determining the laterality of seizure onset zone in frontal lobe epilepsy

Determining the laterality of the seizure onset zone is challenging in frontal lobe epilepsy (FLE) due to the rapid propagation of epileptic discharges to the contralateral hemisphere. There is hemispheric lateralization of autonomic control, and heart rate is modulated by interactions between the sympathetic and parasympathetic nervous systems. Based on this notion, the laterality of seizure foci in FLE might be determined using heart rate variability (HRV) parameters. We explored preictal markers for differentiating the laterality of seizure foci in FLE using HRV parameters. Twelve patients with FLE (6 right FLE and 6 left FLE) were included in the analyzes. A total of 551 (460 left FLE and 91 right FLE) 1-min epoch electrocardiography data were used for HRV analysis. We found that most HRV parameters differed between the left and right FLE groups. Among the machine learning algorithms applied in this study, the light gradient boosting machine was the most accurate, with an AUC value of 0.983 and a classification accuracy of 0.961. Our findings suggest that HRV parameter-based laterality determination models can be convenient and effective tools in clinical settings. Considering that heart rate can be easily measured in real time with a wearable device, our proposed method can be applied to a closed-loop device as a real-time monitoring tool for determining the side of stimulation.

Rabies death in a prisoner: necessity for medical history documentation

Rabies is a zoonotic illness with a high mortality rate that attacks mammals' central nervous systems. It is a viral illness that may be avoided with immunization. Up to 99% of the human rabies transmissions occur in dogs, making them the primary cause of rabies mortality in humans. It is a case-report of rabies death in a 55-years old male, a prisoner from Phulbani Jail (Kandhamal), who was presented to MKCG Medical College and Hospital casualty with with chief complaints of difficulty in breathing and difficulty in drinking water since last night on 17 July 2023, at 11:19 pm. The patient had a history of dog bite exposure four years ago, for which he had not received any post-exposure prophylaxis. The patient was identified as having a likely case of rabies based on his previous history of animal bite and clinical manifestations. Patient was declared dead on 18 July 2023 at 10:30 am. Rabies diagnosis was confirmed by pathological examination of brain sample which showed presence of Negri bodies. This case-report focuses on the importance of proper medical history information including any animal bite exposure especially for convicts before admitting in prison so as to avoid later morbidity and its legal consequences. Such kind of incident also shows that there is lack of awareness regarding rabies in community. In this instance, mortality may have been prevented if the patient had finished the anti-rabies vaccine regimen and made it to a higher center in time for immunoglobulin. Increasing rabies vaccination awareness among the general public can help reduce rabies-related deaths.

Anti-fatigue activity of methyl dihydrojasmonate and linalool in a rat model evaluated by a novel index for neuro-immune and oxidative stress interactions

Avoiding fatigue is a long-standing challenge in both healthy and diseased individuals. Establishing objective standard markers of fatigue is essential to evaluate conditions in spatiotemporally different locations and individuals and identify agents to fight against fatigue. Herein, we introduced a novel method for evaluating fatigue using nervous system markers (including dopamine, adrenaline, and noradrenaline), various cytokine levels (such as interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-10, IL-2, IL-5 and IL-17A), and oxidative stress markers (such as diacron-reactive oxygen metabolites [d-ROMs] and biological antioxidant potential [BAP]) in a rat fatigue model. Using this method, the anti-fatigue effects of methyl dihydrojasmonate (MDJ) and linalool, the fragrance/flavor compounds used in various products, were assessed. Our method evaluated the anti-fatigue effects of the aforementioned compounds based on the changes in levels of the nerves system markers, cytokines, and oxidative stress markers. MDJ exerted more potent anti-fatigue effects than linalool. In conclusion, the reported method could serve as a useful tool for fatigue studies and these compounds may act as effective therapeutic agents for abrogating fatigue symptoms.

Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders

The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.

Probabilistic risk assessment of dietary exposure to lead in residents of Guangzhou, China

Lead and its compounds can have cumulative harmful effects on the nervous, cardiovascular, and other systems, and especially affect the brain development of children. We collected 4918 samples from 15 food categories in 11 districts of Guangzhou, China, from 2017 to 2022, to investigate the extent of lead contamination in commercial foods and assess the health risk from dietary lead intake of the residents. Lead was measured in the samples using inductively coupled plasma mass spectrometry. Dietary exposure to lead was calculated based on the food consumption survey of Guangzhou residents in 2011, and the health risk of the population was evaluated using the margin of exposure (MOE) method. Lead was detected in 76.5% of the overall samples, with an average lead content of 29.4 µg kg−1. The highest lead level was found in bivalves. The mean daily dietary lead intakes were as follows: 0.44, 0.34, 0.25, and 0.28 µg kg−1 body weight (bw) day−1 for groups aged 3–6, 7–17, 18–59, and ≥ 60 years, respectively. Rice and rice products, leafy vegetables, and wheat flour and wheat products were identified as the primary sources of dietary lead exposure, accounting for 73.1%. The MOE values demonstrated the following tendency: younger age groups had lower MOEs, and 95% confidence ranges for the groups aged 3–6 and 7–17 began at 0.6 and 0.7, respectively, indicating the potential health risk of children, while those for other age groups were all above 1.0. Continued efforts are needed to reduce dietary lead exposure in Guangzhou.

Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.

Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein-coupled receptor (GPCR) and a phospholipase C-dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo-EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small-molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small-molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug-like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug-like TRPC3 modulator will be valuable in advancing small-molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small-molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies.

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Neuroimmunological effects of omega-3 fatty acids on migraine: a review

Clinical Experience With Acute Phase Repair of Facial Nerve Dissections.

The purpose of this study was to evaluate the facial nerve recovery of patients with traumatic facial nerve transections after tension-free end-to-end nerve epineural anastomosis during the acute phase. A total of 11 patients with traumatic facial nerve transections during the acute phase were surgically treated in the authors' department from November 2016 to August 2022. The case data and imaging data were collected from the patients, and the House-Brackman evaluation system of the facial nerve was applied to assess the recovery of facial nerve function, and the higher the grade, the worse the facial nerve function. Of the patients, 90.9% recovered to H-B grade II or below, and there were differences in the degree of recovery of the facial nerve function among the branches, and the ones that recovered to H-B grade II or below after surgery were 100% of the zygomatic branch, of which 80% were H-B grade I, 100% of the buccal branch, of which 44.4% were H-B grade I, 88.9% of the marginal mandibular branch, and 66.7% of the temporal branch. The study showed that the recovery rate of young patients was better than that of middle-aged and old people, and the best recovery of each branch of the facial nerve was the zygomatic branch, followed by the buccal branch, the marginal mandibular branch, and the worse was the temporal branch.

Copper Poisoning with Emphasis on Its Clinical Manifestations and Treatment of Intoxication

Background. Copper is an essential trace element found in the human body in an oxidized (Cu II) and reduced (Cu I) form. It plays a crucial role in the integrity and function of proteins and enzymes. Short-term and long-term exposure to copper can result in harmful effects and lead to clinical manifestations in multiple bodily systems, including the gastrointestinal tract, liver, kidneys, eyes, respiratory, cardiovascular, central nervous, endocrine, and hematopoietic systems. Objective. The purpose of this study is the importance of early recognition and diagnosis of copper poisoning immediate and necessary measures and the use of chelators. Materials and Methods. In this review article, authors from Pub Med, Scopus, and a toxicologic emergencies reference book from 1996 to 2024 are used. Result. An excessive increase in copper level produces reactive oxygen species that can cause lipid peroxidation in cell membranes, direct oxidation of proteins, and the breakdown of DNA and RNA molecules. All of these can generally be reasons for cell death. Conclusion. Assessing levels of copper in whole blood, free serum copper, 24-hr urine copper, liver biopsy for copper concentration, and ceruloplasmin play a crucial role in the diagnosis. The blood copper concentration is directly related to the severity of poisoning. Treatment for copper poisoning typically involves removing the source of exposure and administering medications to help remove the excess copper from the body. Supportive care for copper intoxication usually includes managing vomiting, correcting fluids and electrolytes, and stabilizing vital signs. Chelators like D-penicillamine, succimer, trientine, tetrathiomolybdate, and PBT-2 have been utilized in treatment.

A Design and Construction of the Vibration Perception Threshold Measurement Device for Diabetes

The purpose of this study was to design and build a mechanical vibration assessment tool for diabetic patients’ peripheral nervous systems. There is a substantial correlation between peripheral sensory neuropathy and vibration perception threshold (VPT). Peripheral sensory neuropathy has been identified by VPT determination utilizing the VPT measurement instrument built for that purpose. The designed device can assist in determining the threshold and tracking any progressive changes or trends. This designed device consists of two main components: hardware and software. The hardware part includes a DC power supply circuit, an Arduino NANO, a display, an isolation MOSFET driver for the electrical isolation circuit, a transducer driver, and a transducer head. The software part uses C programming on the Arduino to generate signals and display the transducer supply voltage. The testing results consist of 1) the voltage settings results (5–30 volts) comparing the voltage values on the display between the designed device and a digital multimeter, which has an average error of 0.75%, 2) According to the transducer head pressing test results, the Vibrotest Digital Biothesiometer and the proposed device had different pressing weights of ±0.02 g, and 3) the electrical safety testing results of the designed device is in the standard of IEC60601-1. (IEC: International Electrotechnical Commission).

Influence of peripheral nerve system on proliferation and migration of keratinocytes on site of the wound edges

AIM: to assess proliferation and migration of keratinocytes at the nonhealing edges of neuropathic wounds.MATERIALS AND METHODS: 25 patients with neuropathic ulcers and 5 patients without diabetes with decubitus were enrolled. Diabetic foot (DF) patients were underwent to standard treatment including debridement, atraumatic dressing, offloading, antibacterial therapy if it needs. Severity of peripheral neuropathy was assessed according to the NDS scale. Histo­logical (hematoxylin and eosin) and immunohistochemical (Ki-67 , α7nAChR markers) examination of wound edge were done during treatment (0, 10, 24 days).RESULTS: All patients have severe neuropathy according to NDSm (>8). The average size of DF ulcers before and on 10th day of treatment was of 4 cm2 and 2,5 cm2, respectively (p<0,004). Neuropathic ulcers were characterized by hyperproliferative epidermis. Mitotically active keratinocytes reside throughout the suprabasal layers. Ki-67 expressed all layers of the epidermis, but a greater staining density was detected in the basal layer. The density of a7nAChR-positive cells increased from 0 to 24 days (p=0,031).THE CONCLUSION: The data shows that neuropathy is one of the possible mechanisms of keratinocyte cell cycle disruption: proliferative activity and ability to migrate. Identification of new signaling pathways regulating the physiological repair of tissues and the study of their disorders in diabetes mellitus opens the prospect of developing an optimal therapeutic strategy.

Enterococcus faecalis: implications for host health.

The microbiota represents a crucial area of research in maintaining human health due to its potential for uncovering novel biomarkers, therapies, and molecular mechanisms relevant to population identification and experimental model characterization. Among these microorganisms, Enterococcus faecalis, a Gram-positive bacterium found in the gastrointestinal tract of humans and animals, holds particular significance. Strains of this bacterial species have sparked considerable debate in the literature due to their dual nature; they can either be utilized as probiotics in the food industry or demonstrate resistance to antibiotics, potentially leading to severe illness, disability, and death. Given the diverse characteristics of Enterococcus faecalis strains, this review aims to provide a comprehensive understanding of their impact on various systems within the host, including the immunological, cardiovascular, metabolic, and nervous systems. Furthermore, we summarize the bacterium-host interaction characteristics and molecular effects to highlight their targets, features, and overall impact on microbial communities and host health.

The role of environmental sensitivity in the mental health of Syrian refugee children: a multi-level analysis.

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data. Child-caregiver dyads were recruited from informal tented settlements in Lebanon, and completed a battery of psychological instruments at baseline and follow-up (12 months apart). Univariate and multivariate Bayesian linear mixed models were used to examine a) the interrelationships between markers of sensitivity and b) the ability of sensitivity markers to predict anxiety, depression, post-traumatic stress disorder, and externalising behaviour. Self-reported sensitivity (using the Highly Sensitive Child Scale) significantly predicted a higher burden of all forms of mental illness across both waves, however, there were no significant cross-lagged pathways. Physiological and genetic markers were not stably predictive of self-reported sensitivity, and failed to similarly predict mental health outcomes. The measurement of environmental sensitivity may have significant implications for identifying and treating mental illness, especially amongst vulnerable populations, but clinical utility is currently limited to self-report assessment.

Unraveling the genetic architecture of blood unfolded p-53 among non-demented elderlies: novel candidate genes for early Alzheimer's disease

BackgroundAlzheimer's disease (AD) is a heritable neurodegenerative disease whose long asymptomatic phase makes the early diagnosis of it pivotal. Blood U-p53 has recently emerged as a superior predictive biomarker for AD in the early stages. We hypothesized that genetic variants associated with blood U-p53 could reveal novel loci and pathways involved in the early stages of AD.ResultsWe performed a blood U-p53 Genome-wide association study (GWAS) on 484 healthy and mild cognitively impaired subjects from the ADNI cohort using 612,843 Single nucleotide polymorphisms (SNPs). We performed a pathway analysis and prioritized candidate genes using an AD single-cell gene program. We fine-mapped the intergenic SNPs by leveraging a cell-type-specific enhancer-to-gene linking strategy using a brain single-cell multimodal dataset. We validated the candidate genes in an independent brain single-cell RNA-seq and the ADNI blood transcriptome datasets. The rs279686 between AASS and FEZF1 genes was the most significant SNP (p-value = 4.82 × 10–7). Suggestive pathways were related to the immune and nervous systems. Twenty-three candidate genes were prioritized at 27 suggestive loci. Fine-mapping of 5 intergenic loci yielded nine cell-specific candidate genes. Finally, 15 genes were validated in the independent single-cell RNA-seq dataset, and five were validated in the ADNI blood transcriptome dataset.ConclusionsWe underlined the importance of performing a GWAS on an early-stage biomarker of AD and leveraging functional omics datasets for pinpointing causal genes in AD. Our study prioritized nine genes (SORCS1, KIF5C, TMEFF2, TMEM63C, HLA-E, ATAT1, TUBB, ARID1B, and RUNX1) strongly implicated in the early stages of AD.

Unraveling the Connection: Pain and Endoplasmic Reticulum Stress.

Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies.

Metabolic dysfunction-associated steatotic liver disease and atherosclerosis.

To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions. An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes. MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.

Infrared Neuromodulation - a Review.

Infrared (IR) neuromodulation (INM) is an emerging light-based neuromodulation approach that can reversibly control neuronal and muscular activities through the transient and localized deposition of pulsed IR light without requiring any chemical or genetic pre-treatment of the target cells. Though the efficacy and short-term safety of INM have been widely demonstrated in both peripheral and central nervous systems, the investigations of the detailed cellular and biological processes and the underlying biophysical mechanisms are still ongoing. In this review, we discuss the current research progress in the INM field with a focus on the more recently discovered IR nerve inhibition (INI). Major biophysical mechanisms associated with IR nerve stimulation (INS) are summarized. As the INM effects are primarily attributed to the spatiotemporal thermal transients induced by water and tissue absorption of pulsed IR light, temperature monitoring techniques and simulation models adopted in INM studies are discussed. Potential translational applications, current limitations, and challenges of the field will be elucidated to provide guidance for future INM research and advancement.&#xD.