Central Nervous System In Patients Research Articles

Effects of transcranial direct current stimulation and sensorimotor training in anterior cruciate ligament patients: a sham-controlled pilot study.

Studies showed changes in the central nervous system in patients who sustained an anterior cruciate ligament tear. There is a lack of evidence regarding the effectiveness of transcranial direct-current stimulation in such patients. A sham-controlled randomised study. One group of patients (n = 6) underwent 6 weeks of sensorimotor training after an anterior cruciate ligament tear during transcranial direct-current stimulation. The stimulation consisted of 20 minutes (3 sessions/week; 2 weeks) of 2 mA anodal transcranial direct-current stimulation over the primary motor and premotor cortex. The second group (n = 6) received sham stimulation with 6 weeks of sensorimotor training. Centre of pressure deviations in the medio-lateral and anterior-posterior direction and centre of pressure velocity were measured. The results demonstrated a significant effect of sensorimotor training on the centre of pressure in medio-lateral and anterior-posterior direction (p=0.025) (p=0.03) in the leg in which an anterior cruciate ligament tear occurred. The type of training did not affect the results. Post-hoc tests showed no significant effect of training in the subgroups (p≥0.115). Sensorimotor training led to a decrease in sway of the centre of pressure in patients who sustained an anterior cruciate ligament tear, but the addition of anodal transcranial direct-current stimulation placed over the primary motor cortex did not potentiate the adaptive responses of the sensorimotor training.

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer's Disease.

Elevated levels of iron occur in both cortical and subcortical regions of the CNS in patients with Alzheimer's disease. This accumulation is present early in the disease process as well as in more advanced stages. The factors potentially accounting for this increase are numerous, including: (1) Cells increase their uptake of iron and reduce their export of iron, as iron becomes sequestered (trapped within the lysosome, bound to amyloid β or tau, etc.); (2) metabolic disturbances, such as insulin resistance and mitochondrial dysfunction, disrupt cellular iron homeostasis; (3) inflammation, glutamate excitotoxicity, or other pathological disturbances (loss of neuronal interconnections, soluble amyloid β, etc.) trigger cells to acquire iron; and (4) following neurodegeneration, iron becomes trapped within microglia. Some of these mechanisms are also present in other neurological disorders and can also begin early in the disease course, indicating that iron accumulation is a relatively common event in neurological conditions. In response to pathogenic processes, the directed cellular efforts that contribute to iron buildup reflect the importance of correcting a functional iron deficiency to support essential biochemical processes. In other words, cells prioritize correcting an insufficiency of available iron while tolerating deposited iron. An analysis of the mechanisms accounting for iron accumulation in Alzheimer's disease, and in other relevant neurological conditions, is put forward.

Brain Metabolic Correlates of the Off-Target Effects of Enzalutamide on the Central Nervous System of Patients with Advanced Prostate Cancer.

Brain Metabolic Correlates of the Off-Target Effects of Enzalutamide on the Central Nervous System of Patients with Advanced Prostate Cancer.

Entrectinib in the treatment of ROS1-positive lung cancer

The possibilities in the treatment of patients with non–small cell lung cancer are constantly expanding – thanks to high-performance genomic profiling methods, we are discovering new targets in the tumor for drug action, as a result, new targeted drugs appear, some of them have several application points. Multipurpose drugs have a number of advantages and therefore have become the main direction of drug development. Entrectinib is an oral low molecular weight multikinase inhibitor that blocks three targets at once – the receptors of tyrosine kinases ROS1, NTRK1/2/3 and ALK, in 2023 was approved by the Ministry of Health of the Russian Federation for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer. This form of lung cancer is classified as a rare orphan disease, which usually occurs in younger people (about 50 years old), more often in women and non-smokers. Until recently , we had the only active targeted drug – crizotinib. It provided a sufficiently high immediate effect and long-term control of the disease. However, his intracranial activity was not evaluated prospectively, and a retrospective analysis showed modest results. Entrectinib is distinguished from its competitor by high intracranial activity, and, as is known, metastatic brain damage in patients with activating mutations is quite common. With comparable indicators of objective response, its duration and time to progression, entrectinib provides a high level of intracranial control and reduces the risks of progression in the central nervous system in patients who did not have brain metastases at the beginning of therapy. In addition, entrectinib demonstrates good tolerability.

Metastases to lymph nodes from monofocal and multifocal papillary thyroid malignant tumors in patients with autoimmune thyroiditis

The aim of this work was to study the risk factors for metastasis to the central and lateral neck lymph nodes in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), especially in patients with Hashimoto’s thyroiditis (TH).Methods: A retrospective analysis of 763 patients after thyroidectomy with bilateral central lymphadenectomy (CLE) was performed at the interterritorial Center for Endocrine Surgery in Krasnodar during the period from October 2011 to October 2021. All patients had official histological diagnoses of TH. To identify risk factors for metastasis (Mts) to the lymph nodes of the neck, a multifactorial logistic regression analysis was performed.Results: In our study, 277 patients with SCLC and TC showed relatively low rates of Mts to the central lymph nodes (CLU) compared with patients with SCLC without TC (37.2 % vs. 54.7 %, P 140 IU / ml was established as the most sensitive and specific level for predicting MPCT based on the study. Antibodies to AT-TPO, age, tumor size, and multifocal tumor shape demonstrated the ability to predict Mts in the central nervous system in patients with PCT on the background of TC with a probability of 81.1 % based on a multidimensional model. TH was associated with an increased prevalence of multifocal tumor with invasion of the gland capsule.Conclusions: TH detection demonstrated the reduced risk of metastases to the CLN in patients with PCT and MPCT and indicated a potential protective effect. We found that the prognostic model is applicable for predicting a multifocal tumor and metastasis to the central nervous system in patients with PCT and TH.

The relationship between the functional state of the brain and clinical and constitutional factors in schizophrenia

To establish the relationships of functional changes of the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. One hundred and eighteen patients with schizophrenia (64 men and 54 women), aged 33 [29; 40], years were examined. The following clinical and dynamic parameters were used: age of manifestation of the disease, duration of the disease, severity of clinical and psychopathological symptoms according to the PANSS. The anthropometric examination of patients was carried out according to V.V. Bunak's method in V.P. Chitetsov's modification for adult samples with calculation of Rees-Eysenk and Tanner indices. The EEG was recorded and analyzed in a state of calm, relaxed wakefulness with closed eyes with the calculation of the absolute spectral power for theta (4-7 Hz), alpha (8-13 Hz) and beta (14-30 Hz) rhythms. Significant (p<0.05) direct correlations between the age of the disease manifestation and the spectral power of the beta rhythm in the frontal leads (Fp1, Fp2, F3 and F4) were revealed. Inverse correlations (p<0.05) were found between the duration of the disease in patients with schizophrenia and the spectral power of the alpha rhythm in the left temporal (T3) and right central leads (C4), the spectral power of the beta rhythm in the parietal-occipital (P3, P4, O1,O2) and temporal leads (T3, T4, T5), the spectral power of the theta rhythm in the left occipital (O1) and posterior temporal leads (T5). Significant inverse correlations were also found between the Tanner index and the spectral power of the alpha rhythm in the frontal and temporal leads, between the Rees-Eysenk index and the spectral power of the theta rhythm in the frontal leads. The results indicate the presence of the conjugation of functional changes in the brain of patients with schizophrenia with clinical manifestations of the disease and their constitutional and morphological features. Thus, the assessment of the functional state of the central nervous system in patients with schizophrenia is an important component of the diagnostic search.

Hypopituitarism due to CNS Aspergillus Infection.

A 59-year-old man was admitted to our hospital with hyponatremia. An endocrine examination indicated panhypopituitarism, and magnetic resonance imaging revealed a mass-like lesion in the pituitary gland. Sinus endoscopy revealed a fungal mass in the sphenoid sinus, and the patient was diagnosed with hypopituitarism due to aspergillosis of the central nervous system (CNS). The patient's hyponatremia resolved with hydrocortisone replacement. Although the right internal carotid artery was eventually occluded, antifungal medications were administered for the aspergillosis, and the patient's general condition improved. The patient's CNS lesions have remained under control since discharge. This is the first case to suggest that ACTH secretion may be relatively preserved in Aspergillus-induced hypopituitarism.

Assessment of neurofunctional activity in patients with vibration disease caused of local vibration

Introduction. The stressful effect of local vibration contributes to the development of cerebral dysfunction with the formation of a sensorineural deficit in patients with vibration disease associated with exposure to local vibration.&#x0D; The study aims to identify the features of changes in somatosensory evoked potentials, neuroenergocarting and neuropsychological testing in patients with local vibration.&#x0D; Materials and methods. Scientists examined 103 patients with local vibration (group one), 35 healthy men (comparison group). We used methods of registration of somatosensory evoked potentials (SSEP), constant potential level (CPL), neuropsychological testing.&#x0D; Results. The authors revealed in the first group, in comparison with the other group, a significant increase in cerebral energy metabolism in the form of an increase in the level of constant potential in the frontal right and left (Fd, Fs), central (Cd, Cz, Cs), parietal (Pd, Pz, Ps), occipital (Oz), right and central temporal (Td, Tz) brain regions, increased latency of peaks N10, N11, N13, N30, peak interval N13–N18 at p&lt;0.04, cognitive dysfunction with mild damage to prefrontal frontal lobes, inferior temporal and inferior parietal regions, parietal-temporal-occipital zone of the left hemisphere, as well as subcortical structures. The data of the correlation analysis indicate that the slowing down of the ascending somatosensory flow from the level of the brachial plexus ganglia to the ventroposterolateral nucleus of the thalamus contributes to the emergence of a compensatory state in the form of an increase in energy processes in the frontal-central and parietal parts of the cerebral cortex, causing the development of cognitive disorders.&#x0D; Limitations. The limitations of the study were the lack of studying the effects of local vibration on cerebral hemodynamics and the state of efferent pathways of the central nervous system in patients with local vibration.&#x0D; Conclusion. Signs of impaired neurofunctional activity in local vibration are an increase in the duration of peak intervals N10–N13 and N11–N13, the latency of peak N10, the level of constant potential of the frontal right and central left leads, the level of constant potential of interhemispheric relations in the central department, a decrease in categorical and conceptual thinking, short-term (auditory) memory, visual gnosis, expressive speech.&#x0D; Ethics. The study was conducted in compliance with Ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical principles of conducting scientific medical research with human participation" as amended in 2000 and "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation No. 266 dated 06/19/2003. Informed consent was received from each person to participate in the survey, approved in accordance with the established procedure by the Local Ethics Committee.

Anti-GAD encephalitis in a child with beta-thalassemia after allogeneic hematopoietic stem cell transplantation

Glutamic acid decarboxylase (GAD) is an intracellular enzyme expressed in brain neurons and insulin-secreting β-cells of the pancreas. Anti-GAD-anitibodies are associated with type 1 diabetes mellitus, limbic encephalitis, cerebellar ataxia, temporal autoimmune epilepsy, and rigid man syndrome. We present a rare clinical case of anti-GAD-anitibodies- associated immune encephalitis in a child with beta-thalassemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).A 3-year-old boy diagnosed with beta-thalassemia underwent allo-HSCT from a 9/10 compatible unrelated donor. The macrophage activation syndrome occurred during the early post-transplantation period. The seizure with a focal onset happened on day +65. The cytotoxic edema in the region of the left hippocampus without signs of accumulation of a contrast agent was revealed at the magnetic resonance imaging of the brain. Pleocytosis, increase in protein levels, infection and antibodies to receptors and synaptic proteins of neurons were not detected at the analysis of cerebrospinal fluid. A positive titer to anti-GAD-anitibodies was detected in the blood – 315.82 IU/ml (the norm is up to 10 IU/ml). The child was treated with cyclophosphamide 750 mg/m2, rituximab 375 mg/m2, and tocilizumab 8 mg/kg. The cytotoxic edema in the left hippocampus regressed at the control magnetic resonance imaging on day +117.Infectious, immune and toxic agents can cause the damage of central nervous system in patients after allo-HSCT. The mechanism of immune damage to the central nervous system S in such patients is still being studied and may be different: expansion of autoreactive lymphocytes due to failure of T-cell regulation due to chemo- or immunosuppressive therapy, “passenger lymphocyte” syndrome, violation of T-cell regulation due to the course of infectious complications and acute graft versus host disease.In a series of diagnostic searches in patients with central nervous system lesions after allo-HSCT, it is necessary to include immune damage to the nervous system. Diagnosis of such conditions is a difficult task due to comorbidity and multicomponent accompanying therapy, including immunosuppressive therapy, administered to patients.

Transcranial pulse stimulation (TPS) as a method for treating the central nervous system of patients with Alzheimer’s disease

AbstractBackgroundDementia ‐ one of the most common diseases in old age ‐ is often only diagnosed at a late stage. Therefore patients with dementia have often a 1.4 to 3.6 times greater risk of treatment as an inpatient. Consequently it is highly relevant within the caring system to identify and treat the onset of dementia at the earliest possible opportunity.Part of a new treatment center, a psychiatric clinic in the Hanover area (Wahrendorff) has concentrated on treating patients with a mild or moderate form of Alzheimer’s disease as early as possible on an outpatient basis. The method of transcranial pulse stimulation (TPS®) with the Neurolith® system is used. Acoustic pulses generated outside the body are introduced specifically into the brain regions requiring treatment. The aim being the release of growth factors and an improvement in cerebral blood flow, as a means of maintaining and promoting cognitive performance for as long as possible. The poster contribution shows reports from clinicians, patients and relatives, using TPS®. The development of cognitive performance in the course of treatment is also considered.MethodThe data collection for the quantitative study design will take place at the clinic in the period from 06/2021 to 10/2022 (N = 61). Cognitive performance is recorded using the Montreal Cognitive Assessment (MoCA test) and the experience reports via interview.ResultResults of repeated measurement and analysis of the variance in terms of cognitive performance (MoCA test, baseline and follow‐up measures) showed cognitive improvements.ConclusionTranscranial pulse stimulation is a new and promising approach in the treatment of Azheimer’s disease.

Differences in Cortical Activation During Dorsiflexion and Plantarflexion in Chronic Ankle Instability: A Task-fMRI Study.

Chronic ankle instability is a common sports injury that often presents with increased plantarflexion and restricted dorsiflexion. The cumulative effect of peripheral injuries may induce neuroplasticity in the central nervous system. However, the relationship between dorsiflexion or plantarflexion and the central nervous system in patients with chronic ankle instability remains unknown. (1) Is there a difference in region and voxel (volume pixel) of cortical activation during plantarflexion and dorsiflexion between patients with chronic ankle instability and a control group with normal ankle function? (2) Is there a correlation between activation of sensorimotor-related brain regions and three clinical measurement scales of ankle function and disease severity in patients with chronic ankle instability? Between December 2020 and May 2022, we treated 400 patients who had chronic ankle instability. Ten percent (40 patients; mean ± standard deviation age 29 ± 7 years; 17 male patients) were randomly selected to participate in this study. We recruited 42 volunteers with normal ankle function (mean age 28 ± 5 years; 21 male participants) matched by age and education level. A total of 2.5% (1 of 40) of patients with bilateral chronic ankle instability and 30% (12 of 40) with left-sided chronic ankle injury did not meet our inclusion criteria and were excluded from the study. The control group underwent MRI with good image quality. Finally, 27 patients with chronic ankle instability (mean age 26 ± 5 years; 10 male patients) and 42 participants with normal ankle function were enrolled. Ankle function and disease severity were assessed using three clinical scales: the Cumberland Ankle Instability Tool, Karlsson-Peterson Ankle Function Score, and the American Orthopedic Foot and Ankle Society Score. A uniplanar and nonweightbearing ankle dorsiflexion-plantarflexion paradigm (a recognized model or pattern) was performed using a short-block design during the functional MRI scan. This experimental design included a series of on-off periods consisting of movement and a rest period. From 15° of plantarflexion to 15° of dorsiflexion, the manipulator allowed 30° of ankle rotation. The cerebral excitability patterns between patients with chronic ankle instability and controls were analyzed using t-tests. We retained voxels with p values less than 0.05 in a voxel-level family-wise error correction. Clusters with voxel numbers greater than 10 were retained. The Cohen d coefficient was used to calculate between-group effect sizes. Spearman analysis was performed to explore the correlation between activation regions and the three clinical assessment scales. In the patient group, cortical activation was greater during plantarflexion than during dorsiflexion, which was different from that in the control group. The between-group comparison showed that patients with chronic ankle instability had reduced activation in the ipsilateral precuneus (cluster size = 35 voxels [95% CI -0.23 to 0.07]; p < 0.001) during dorsiflexion, whereas during plantarflexion, chronic ankle instability caused increased activation in the ipsilateral superior temporal gyrus (cluster size = 90 voxels [95% CI -0.73 to -0.13]; p < 0.001), precuneus (cluster size = 18 voxels [95% CI -0.56 to -0.19]; p < 0.001), supplementary motor area (cluster size = 57 voxels [95% CI -0.31 to 0.00]; p < 0.001), superior frontal gyrus (cluster size = 43 voxels [95% CI -0.82 to -0.29]; p < 0.001), medial part of the superior frontal gyrus (cluster size = 39 voxels [95% CI 0.41 to 0.78]; p < 0.001), and contralateral postcentral gyrus (cluster size = 100 voxels [95% CI -0.32 to 0.02]; p < 0.001). Patients with chronic ankle instability showed a large effect size compared with controls (Cohen d > 0.8). During plantarflexion, the number of activated voxels in the supplementary motor area had a modest, positive correlation with the Karlsson-Peterson Ankle Function Score (r = 0.52; p = 0.01), and the number of activated voxels in the primary motor cortex (M1) and primary sensory cortex (S1) had a weak, positive correlation with the American Orthopedic Foot and Ankle Society Score in patients with chronic ankle instability (M1: r = 0.45; p = 0.02, S1: r = 0.49; p = 0.01). Compared with volunteers with normal ankle function, patients with chronic ankle instability had increased cortical activation during plantarflexion and decreased cortical activation during dorsiflexion. We analyzed the central neural mechanisms of chronic ankle instability in patients with sports injuries and provided a theoretical basis for the development of new central and peripheral interventions in the future. Because there was a positive correlation between the neural activity in sensorimotor-related regions during plantarflexion and clinical severity, clinicians might one day be able to help patients who have chronic ankle instability with neuromuscular rehabilitation by applying electrical stimulation to specific targets (such as S1M1 and the supplementary motor area) or by increasing activation of sensorimotor neurons through ankle movement.

Research advances on mental disorders in patients with extensive burns

Extensive burns can cause nonnegligible acute and chronic damage to central nervous system of patients. The damage of central nervous system may have a profound impact on patients, including neurobehavioral changes such as post-traumatic stress disorder, depression, anxiety, and sleep disorder. These changes may persist after injury, greatly affecting patients' integration into society and return to work. This paper systematically reviewed the clinical manifestations, pathogenesis, and current intervention methods of mental disorders in patients with extensive burns, aiming to provide a basis for further understanding, prevention, and treatment of patients with mental disorders after burns.

Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic.

Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted receptors, altering synaptic communication. The importance to clarify, in preclinical models, the molecular mechanisms involved in the autoantibody-mediated effects has emerged in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. In this review, we describe some of the available preclinical literature concerning the impact of antibodies recognizing NMDA and AMPA receptors in neurons. This review discusses the cellular events that would support the detrimental roles of the autoantibodies, also illustrating some contrasting findings that in our opinion deserve attention and further investigations before translating the preclinical observations to clinic.

One case of acute poisoning with stramonium

This paper reported 1 case of poisoning caused by stramonium. Cases of Datura poisoning have been reported nationwide, Its effect on the central nervous system of patients is characterized by first excitation and then inhibition, clinical manifestations include decreased gland secretion, dilated pupils, and tachycardia, etc. Its poisoning mechanism is anticholinergic effect, the effect on Peripheral nervous system is to inhibit Parasympathetic nervous system. Hemoperfusion combined with neostigmine anticholinergic therapy at the early stage of poisoning can effectively improve the clinical symptoms of patients in a short time.

Cognitive training as a technology for protecting and restoring the functions of the central nervous system in patients with infectious pathology

Cognitive training as a technology for protecting and restoring the functions of the central nervous system in patients with infectious pathology

Donor bone marrow–derived macrophage engraftment into the central nervous system of patients following allogeneic transplantation

AbstractHematopoietic stem cell transplantation is a well-known treatment for hematologic malignancies, wherein nascent stem cells provide regenerating marrow and immunotherapy against the tumor. The progeny of hematopoietic stem cells also populate a wide spectrum of tissues, including the brain, as bone marrow–derived macrophages similar to microglial cells. We developed a sensitive and novel combined immunohistochemistry (IHC) and XY fluorescence in situ hybridization assay to detect, quantify, and characterize donor cells in the cerebral cortices of 19 female patients who underwent allogeneic stem cell transplantation. We showed that the number of male donor cells ranged from 0.14% to 3.0% of the total cells or from 1.2% to 25% of microglial cells. Using tyramide-based fluorescent IHC, we found that at least 80% of the donor cells expressed the microglial marker ionized calcium-binding adapter molecule-1, consistent with bone marrow–derived macrophages. The percentage of donor cells was related to pretransplantation conditioning; donor cells from radiation-based myeloablative cases averaged 8.1% of microglial cells, whereas those from nonmyeloablative cases averaged only 1.3%. The number of donor cells in patients conditioned with busulfan- or treosulfan-based myeloablation was similar to that in total body irradiation-based conditioning; donor cells averaged 6.8% of the microglial cells. Notably, patients who received multiple transplantations and those with the longest posttransplantation survival had the highest level of donor engraftment, with donor cells averaging 16.3% of the microglial cells. Our work represents the largest study characterizing bone marrow–derived macrophages in patients after transplantation. The efficiency of engraftment observed in our study warrants future research on microglial replacement as a therapeutic option for disorders of the central nervous system.

Jamming Enabled Variable Stiffness Wrist Exoskeleton for Tremor Suppression

Parkinson's disease is a chronic disorder that affects the central nervous system of patients. It affects millions of aging populations around the world every year. Approximately 80% of Parkinson's disease patients suffer from tremors which significantly reduce their life quality. In this study, we present a variable stiffness wrist exoskeleton (VSW-Exo) that is lightweight (less than 300 g on the wrist) and can effectively suppress wrist tremors in all three degrees of freedom. The functioning material of the variable stiffness unit is a novel chain mail-like structured fabric whose stiffness can be pneumatically controlled over a wide range under the jamming transition. Bending and Torsion tests are performed to characterize the VSW-Exo's damping force and torque. To evaluate the VSW-Exo's performance on human bodies, we devise vibration experiments to evaluate the prototype's performance on tremor suppression. The testing results show that our VSW-Exo's tremor suppression efficiency can reach up from 64.11 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 10.92% to 67.24 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 6.74%. Compared to other tremor suppression devices, our VSW-Exo can provide enough damping forces and torques to suppress tremors in all 3 directions with high efficiency and low weight on the wrist.

The neurotoxic branch of the kynurenine pathway is highly activated in the central nervous system of patients with pneumococcal meningitis

BackgroundAcute bacterial meningitis (ABM) causes excessive activation of N-methyl-D-aspartate receptors (NMDAr), leading to cortical and hippocampal neuron death. As opposite, enteroviral meningitis is more frequently benign. The kynurenine (KYN) pathway is the major catabolic route of tryptophan (TRP) and some of its metabolites are agonists or antagonists of NMDAr. MethodsIn order to investigate the pathogen-specific patterns of KYN pathway modulation in the central nervous system of children with acute meningococcal (MM), pneumococcal (PM) or enteroviral (VM) meningitis, the cerebrospinal fluid (CSF) concentrations of TRP, KYN, kynurenic acid (KYNA) and quinolinic acid (QUINA) were evaluated by ultra-high performance liquid chromatography (uHPLC) coupled to mass spectrometry. In addition, CSF levels of IL-6, IL-10 and TNF-α were quantified by multi-analyte flow assay. The data was mined and integrated using statistical and machine learning methods. ResultsThe three forms of meningitis investigated herein up-regulated the neurotoxic branch of the KYN pathway within the intrathecal space. However, this response, represented by the concentration of QUINA, was six and nine times higher in PM patients compared to MM or VM, respectively. CSF levels of IL-6, TNF-α, and IL-10 were increased in MM and PM patients when compared to controls. In VM, CSF IL-6 and IL-10, but not TNF-α were increased compared to controls, although not reaching the high levels found in bacterial meningitis. No correlation was found between the concentrations or the ratios of any pair of KYN metabolites and any cytokine or standard cytochemical parameter tested. ConclusionsCNS infection with meningococci, pneumococci, and enteroviruses intrathecally activate the KYN pathway, favoring its neurotoxic branch. However, in PM, higher CSF levels of QUINA, compared to MM and VM, may contribute to its poorer neurologic outcome.

Hydrogen regulates mitochondrial quality to protect glial cells and alleviates sepsis-associated encephalopathy by Nrf2/YY1 complex promoting HO-1 expression.

Sepsis-associated encephalopathy (SAE) is a complication of the central nervous system in patients with sepsis. Currently, no effective treatment for sepsis is available. Hydrogen plays a protective role in different diseases; however, the detailed mechanism of hydrogen-treated disease remains unclear. The purpose of this study was to investigate the effect of hydrogen on SAE in vitro and in vivo and the mechanism of hydrogen in mitochondrial dynamics and its function in astrocytes and microglia stimulated by lipopolysaccharides (LPSs). Animal models of SAE were generated by cecal ligation and puncture, and the SAE model was established by in vitro LPS stimulation. MTT, lactate dehydrogenase (LDH), reactive oxygen species (ROS), heme oxygenase-1 (HO-1) activity, mitochondrial membrane potential (MMP), and cell apoptosis assays were used to determine the effect of hydrogen on astrocytes and microglia stimulated by LPSs. The relationships between nuclear factor erythroid 2-related factor 2 (Nrf2), YY1, and HO-1 were examined by chromatin immunoprecipitation and co-immunoprecipitation. Mitochondrial homeostasis-related proteins in LPS-stimulated glial cells and brain tissues of SAE mice were detected by western blotting. The effects of hydrogen treatment in the SAE mouse model were investigated using Morris water maze and Y-maze analyses. After performing experiments with different concentrations of LPSs in vitro, we selected 1000ng/ml for subsequent experiments. Hydrogen attenuated the increase in ROS, LDH, and apoptosis and promoted decreases in cell activity and MMP, further promoting an increase in HO-1 expression induced by LPSs in astrocytes and microglia. Moreover, hydrogen further promoted the expression of Nrf2, HO-1, PGC-1α, TFAM, PARKIN, and PINK1, inhibited LPS-induced OPA1 and MFN2 expression in astrocytes and microglia, and downregulated the expression of DRP1 after LPS induction. Intriguingly, hydrogen treatment enhanced the binding between Nrf2 and YY1. However, silencing Nrf2 or YY1 abolished the protective effects of hydrogen on cell activity, LDH, ROS, and MMP; apoptosis; and regulation of Nrf2, HO-1, PGC-1α, TFAM, OPA1, DRP1, MFN2, PARKIN, and PINK1 in microglia. Finally, hydrogen treatment improved the results of behavioral detection, apoptosis, Nrf2, HO-1, PGC-1α, TFAM, OPA1, DRP1, MFN2, PARKIN, PINK1, and cytokines in SAE in vivo. Hydrogen improved cell injury and mitochondrial quality, which were associated with HO-1 expression promoted by the Nrf2/YY1 complex in vitro. Thus, hydrogen treatment may represent a novel therapeutic method for treating SAE.

Pharmacodynamic effect of gabapentin on central nervous system in patients with chronic low back pain: a [99mTc]Tc-ECD SPECT study

BackgroundGabapentin is an effective therapeutic alternative for chronic low back pain, indicated in several guidelines for treating neuropathic pain as first-line medication. This study aimed to describe the pharmacodynamics of...