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Communications Biology Jul 2024Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite...
Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.
Topics: Animals; Humans; Adipose Tissue, Brown; Neuroinflammatory Diseases; Bone Marrow; Mice; Male; Glioblastoma; Mice, Inbred C57BL; Female; Multiple Sclerosis; Positron-Emission Tomography
PubMed: 38951146
DOI: 10.1038/s42003-024-06494-x -
Zhonghua Nei Ke Za Zhi Jul 2024To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive...
To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all <0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all <0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all <0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all <0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all <0.01), and right nucleus accumbens (<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (=0.45, =0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (=0.45, =0.047) and information processing speed impairment (=0.50, =0.026). Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.
Topics: Humans; Gray Matter; Cross-Sectional Studies; Multiple Sclerosis; Atrophy; Magnetic Resonance Imaging; Cognition; Cognitive Dysfunction; Cerebral Cortex; Neuropsychological Tests; Male; Female
PubMed: 38951090
DOI: 10.3760/cma.j.cn112138-20231129-00350 -
Neuroscience and Biobehavioral Reviews Jun 2024Multiple sclerosis (MS) is an autoimmune disease, governed by oligodendrocyte (OL) dystrophy and central nervous system (CNS) demyelination manifesting variable... (Review)
Review
Multiple sclerosis (MS) is an autoimmune disease, governed by oligodendrocyte (OL) dystrophy and central nervous system (CNS) demyelination manifesting variable neurological impairments. Mitochondrial mechanisms may drive myelin biogenesis maintaining the axo-glial unit according to dynamic requisite demands imposed by the axons they ensheath. The promotion of OL maturation and myelination by actively transporting thyroid hormone (TH) into the CNS and thereby facilitating key transcriptional and metabolic pathways that regulate myelin biogenesis is fundamental to sustain the profound energy demands at each axo-glial interface. Deficits in regulatory functions exerted through TH for these physiological roles to be orchestrated by mature OLs, can occur in genetic and acquired myelin disorders, whereby mitochondrial efficiency and eventual dysfunction can lead to profound oligodendrocytopathy, demyelination and neurodegenerative sequelae. TH-dependent transcriptional and metabolic pathways can be dysregulated during acute and chronic MS lesion activity depriving OLs from critical acetyl-CoA biochemical mechanisms governing myelin lipid biosynthesis and at the same time altering the generation of iron metabolism that may drive ferroptotic mechanisms, leading to advancing neurodegeneration.
PubMed: 38950685
DOI: 10.1016/j.neubiorev.2024.105788 -
Journal of Managed Care & Specialty... Jul 2024Patient-reported outcomes (PROs) are often used by clinicians to evaluate patient response to specialty medications used to treat multiple sclerosis (MS) and...
BACKGROUND
Patient-reported outcomes (PROs) are often used by clinicians to evaluate patient response to specialty medications used to treat multiple sclerosis (MS) and rheumatologic conditions. Identifying associations among PROs and patient characteristics could inform patient-centered treatment monitoring.
OBJECTIVE
To examine the association among patient characteristics and PROs, including patient-reported adherence (defined as no missed doses), medication tolerance, patient perceived effectiveness, and health care resource utilization (HCRU; defined as emergency department visits or hospitalizations), for patients prescribed specialty medications in 2 health system specialty pharmacies.
METHODS
A dual-center, retrospective review of monthly medication assessments completed by Vanderbilt Specialty Pharmacy and University of Illinois Hospital and Health Sciences System specialty pharmacy was conducted. Patients were included if they received at least 3 fills of a specialty medication from rheumatology or MS clinics from October 2019 to March 2022, excluding patients with more than a 30-day supply. Primary outcomes were the PROs of patient-reported adherence, medication tolerability, perceived effectiveness, and HCRU. For each of the 2 primary outcomes (adherence and tolerability), a mixed-effects logistic regression model was used to test for associations with age, sex, race, clinic, site, and the other PROs.
RESULTS
A total of 61,926 assessments were completed from 3,677 patients (Site 1 = 3,346; 91.0% and Site 2 = 331; 9.0%). Patients were predominantly White (75.6%) and female (71.7%) with a median age of 50 years (IQR = 37-61). Assessments most frequently originated from rheumatology (76.0%). Nonadherence was reported 4.0% of the time, with the most common explanations being forgetfulness (33.1%) and medication being held because of a procedure or illness (29.5%). Most responses indicated perceived effectiveness as good/excellent (93.9%), with 98.5% of responses indicating no issues with tolerability. Patients who reported tolerability issues were 2.5 times more likely to report a missed dose (95% CI = 1.87-3.23, < 0.001). An effectiveness rating of fair was associated with a 61% increase in the odds of a missed dose compared with a rating of good/excellent (95% CI = 1.33-1.94).
CONCLUSIONS
Patients filling rheumatology or MS specialty medications within health system specialty pharmacies reported high rates of medication effectiveness and adherence and low rates of issues with tolerability and HCRU. Patients who report tolerability issues or lower perceived effectiveness may benefit from additional monitoring to prevent nonadherence.
Topics: Humans; Female; Male; Patient Reported Outcome Measures; Middle Aged; Medication Adherence; Retrospective Studies; Adult; Multiple Sclerosis; Aged; Rheumatic Diseases
PubMed: 38950163
DOI: 10.18553/jmcp.2024.30.7.710 -
Cureus May 2024Optic neuritis (ON) is a rare condition in the pediatric age group. Patients with optic neuritis can manifest with a wide range of drops in vision, ranging from mild...
Optic neuritis (ON) is a rare condition in the pediatric age group. Patients with optic neuritis can manifest with a wide range of drops in vision, ranging from mild loss to complete loss of vision. Knowing the cause of optic neuritis is an important point that will affect management and prognosis. Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody is an autoantibody that causes demyelination of the central nervous system (CNS). Treatment with a high dose of IV steroids followed by oral steroids is the best regimen that shows a favorable vision outcome. We aim to report this case of isolated optic neuritis with a positive anti-myelin oligodendrocyte glycoprotein antibody to highlight the prognosis of myelin oligodendrocyte glycoprotein disease with isolated optic neuritis and how early diagnosis and treatment can affect the visual outcome.
PubMed: 38947608
DOI: 10.7759/cureus.61371 -
Frontiers in Immunology 2024Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.
Topics: Humans; Female; Ovarian Neoplasms; Middle Aged; Neuromyelitis Optica; Aquaporin 4; Dysgerminoma; Autoantibodies; Magnetic Resonance Imaging
PubMed: 38947316
DOI: 10.3389/fimmu.2024.1424243 -
Current Tropical Medicine Reports Dec 2023This review aims to elucidate the etiologies of brain abscesses in the tropics. Despite the similarities in causes of brain abscesses across global regions, tropical...
PURPOSE OF REVIEW
This review aims to elucidate the etiologies of brain abscesses in the tropics. Despite the similarities in causes of brain abscesses across global regions, tropical settings manifest distinguishing characteristics, prominently observed on computed tomography or magnetic resonance imaging.
RECENT FINDINGS
In tropical climates, the leading conditions predisposing individuals to brain abscesses are polymicrobial bacterial infections originating from paranasal sinuses, dental sources, and otitis media. However, the tropics present unique etiologies to be aware of, including (Chagas disease), free-living amoebas like , infections from (melioidosis), fungi such as , and . Given the differential diagnoses, which include neoplastic, inflammatory, and demyelinating diseases, a stereotactic biopsy coupled with a microbiological assessment remains valuable for accurate diagnosis.
SUMMARY
In tropical regions, brain abscesses are a concern when confronted with mass-occupying or other types of brain lesions. Successful clinical management of brain abscesses typically combines surgical intervention and extended anti-microbial treatment. However, specific parasitic invasions like Chagas disease, free-living amoebas, and necessitate targeted anti-parasitic therapies. Furthermore, international policy efforts should focus on prevention measures in resource limited regions with heightened risks and disease burden.
PubMed: 38947183
DOI: 10.1007/s40475-023-00306-8 -
The Yale Journal of Biology and Medicine Jun 2024Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and...
Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and impacted by the metabolic implications of diabetes. Insulin receptors, glucose transporters, Na and K channels, and mitochondria are abundant in nodes, all of which have been linked to the development and progression of Diabetic Peripheral Neuropathy (DPN) and Type 1 Diabetes Mellitus (T1DM)-associated cognitive impairment. Our study aimed to evaluate if the administration of (NS) and (CA) prevented diabetes-associated nervous system deficits in hyperglycemic mice. We developed T1DM mice through Streptozotocin (STZ) injections and validated the elevations in blood glucose levels. NS and CA were administered immediately upon the induction of diabetes. Behavioral analysis, histopathological evaluations, and assessment of molecular biomarkers (NR2A, MPZ, NfL) were performed to assess neuropathy and cognitive impairment. Improvements in memory, myelin loss, and the expression of synaptic proteins, even with the retention of hyperglycemia, were evident in the mice who were given a dose of herbal products upon the detection of hyperglycemia. NS was more beneficial in preventing memory impairments, demyelination, and synaptic dysfunction. The findings indicate that including these herbs in the diets of diabetic as well as pre-diabetic patients can reduce complications associated with T1DM, notably diabetic peripheral neuropathy and cognitive deficits associated with T1DM.
Topics: Animals; Diabetic Neuropathies; Nigella sativa; Mice; Cognitive Dysfunction; Male; Diabetes Mellitus, Experimental; Plant Extracts; Plants, Medicinal; Senna Plant
PubMed: 38947105
DOI: 10.59249/UQLO8012 -
Experimental Dermatology Jul 2024The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP)....
The 16th non-collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%-90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti-BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti-NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His-tagged proteins covering the entire BP180 ectodomain (BP180(ec)1-4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A-negative pemphigoid patients.
Topics: Humans; Parkinson Disease; Collagen Type XVII; Non-Fibrillar Collagens; Pemphigoid, Bullous; Autoantigens; Multiple Sclerosis; Autoantibodies; Pemphigoid, Benign Mucous Membrane; Immunoglobulin G; Epitopes; Protein Domains; Female; Male; Aged
PubMed: 38946225
DOI: 10.1111/exd.15125 -
Brain Pathology (Zurich, Switzerland) Jun 2024Demyelination of corticospinal tract neurons contributes to long-term disability after cortical stroke. Nonetheless, poststroke myelin loss has not been addressed as a...
Demyelination of corticospinal tract neurons contributes to long-term disability after cortical stroke. Nonetheless, poststroke myelin loss has not been addressed as a therapeutic target, so far. We hypothesized that an antibody-mediated inhibition of the Nogo receptor-interacting protein (LINGO-1, leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein) may counteract myelin loss, enhance remyelination and axonal growth, and thus promote functional recovery following stroke. To verify this hypothesis, mice were subjected to photothrombotic stroke and received either an antibody against LINGO-1 (n = 19) or a control treatment (n = 18). Behavioral tests were performed to assess the effects of anti-LINGO-1 treatment on the functional recovery. Seven weeks after stroke, immunohistochemical analyses were performed to analyze the effect of anti-LINGO-1 treatment on myelination and axonal loss of corticospinal tract neurons, proliferation of oligodendrocytes and neurogenesis. Anti-LINGO-1 treatment resulted in significantly improved functional recovery (p < 0.0001, repeated measures analysis of variance), and increased neurogenesis in the hippocampus and subventricular zone of the ipsilateral hemisphere (p = 0.0094 and p = 0.032, t-test). Notably, we observed a significant increase in myelin (p = 0.0295, t-test), platelet-derived growth factor receptor α-positive oligodendrocyte precursor cells (p = 0.0356, t-test) and myelinating adenomatous polyposis coli-positive cells within the ipsilateral internal capsule of anti-LINGO-1-treated mice (p = 0.0021, t-test). In conclusion, we identified anti-LINGO-1 as the first neuroregenerative treatment that counteracts poststroke demyelination of corticospinal tract neurons, presumably by increased proliferation of myelin precursor cells, and thereby improves functional recovery. Most importantly, our study presents myelin loss as a novel therapeutic target following stroke.
PubMed: 38946137
DOI: 10.1111/bpa.13280