scholarly journals Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Noriko Shinjyo ◽  
Kiyoshi Kita
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Energy Metabolism ◽  
Cns Infection ◽  
Brain Disorders ◽  
Leptin Signaling ◽  
Metabolic Dysregulation ◽  
Infection Susceptibility ◽  
Metabolic Imbalance ◽  
The Brain

Metabolic syndromes are frequently associated with dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and cognitive impairment. In addition, growing evidence suggests the link between infections and brain disorders, including Alzheimer’s disease. The immune system and energy metabolism are in an intricate relationship. Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced CNS infection susceptibility. Thus, infection and metabolic imbalance can be intertwined to each other in the etiology of brain disorders, including dementia. Insulin and leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and obesity, which are characterized by insulin resistance and leptin signaling deficiency. Examples include human immunodeficiency virus (HIV) infection and periodontal disease caused by an oral pathogen Porphyromonas gingivalis. This review explores potential interactions between infectious agents and insulin and leptin signaling pathways, and discuss possible mechanisms underlying the relationship between infection, metabolic dysregulation, and brain disorders, particularly focusing on the roles of insulin and leptin.

scholarly journals Priming of CD8+ T Cells during Central Nervous System Infection with a Murine Coronavirus Is Strain Dependent

2008 ◽  
Vol 82 (13) ◽  
pp. 6150-6160 ◽  
Author(s):  
Katherine C. MacNamara ◽  
Susan J. Bender ◽  
Ming Ming Chua ◽  
Richard Watson ◽  
Susan R. Weiss
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cns Infection ◽  
Cervical Lymph Nodes ◽  
T Cell Priming ◽  
The Brain

ABSTRACT Virus-specific CD8+ T cells are critical for protection against neurotropic coronaviruses; however, central nervous system (CNS) infection with the recombinant JHM (RJHM) strain of mouse hepatitis virus (MHV) elicits a weak CD8+ T-cell response in the brain and causes lethal encephalomyelitis. An adoptive transfer model was used to elucidate the kinetics of CD8+ T-cell priming during CNS infection with RJHM as well as with two MHV strains that induce a robust CD8+ T-cell response (RA59 and SJHM/RA59, a recombinant A59 virus expressing the JHM spike). While RA59 and SJHM/RA59 infections resulted in CD8+ T-cell priming within the first 2 days postinfection, RJHM infection did not lead to proliferation of naïve CD8+ T cells. While all three viruses replicated efficiently in the brain, only RA59 and SJHM/RA59 replicated to appreciable levels in the cervical lymph nodes (CLN), the site of T-cell priming during acute CNS infection. RJHM was unable to suppress the CD8+ T-cell response elicited by RA59 in mice simultaneously infected with both strains, suggesting that RJHM does not cause generalized immunosuppression. RJHM was also unable to elicit a secondary CD8+ T-cell response in the brain following peripheral immunization against a viral epitope. Notably, the weak CD8+ T-cell response elicited by RJHM was unique to CNS infection, since peripheral inoculation induced a robust CD8+ T-cell response in the spleen. These findings suggest that the failure of RJHM to prime a robust CD8+ T-cell response during CNS infection is likely due to its failure to replicate in the CLN.

scholarly journals Serum Procalcitonin Levels in Patients with Acute Central Nervous System Infections

2020 ◽  
Vol 8 (B) ◽  
pp. 1251-1255
Author(s):  
Yordan Kalchev ◽  
Tsetsa Petkova ◽  
Ralitsa Raycheva ◽  
Bothwell Kabayira ◽  
Tanya Deneva ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Bacterial Infections ◽  
Clinical Symptoms ◽  
Discriminatory Power ◽  
Cns Infection ◽  
Microbiological Analysis ◽  
Significant Difference ◽  
Serum Crp ◽  
The Brain

BACKGROUND: Bacterial infections of the brain are associated with high mortality and neurological sequelae, whereas viral diseases are usually self-limiting. A fast and easy-to-perform biomarker is needed to improve management in these patients. AIM: Procalcitonin (PCT) testing has already been implemented in many laboratories for evaluating septic patients and it is an easily accessible biomarker, so we aimed to examine its role specifically in discriminating acute bacterial from viral infections of the central nervous system (CNS). MATERIALS AND METHODS: This prospective study included 80 patients with both clinical symptoms and laboratory findings suggesting acute CNS infection. The microbiological analysis included direct microscopy, culturing, latex-agglutination test, and multiplex polymerase chain reaction. PCT levels were measured by enzyme-linked fluorescent assay technology. RESULTS: Following the results of the microbiological analysis, the cases were divided into three groups – bacterial 26.3% (n = 21), viral 17.5% (n = 14), and unidentified neuroinfections – 56.2% (n = 45). A statistically significant difference in the median serum PCT was observed between the bacterial and viral neuroinfections (p = 0.004) as well as between bacterial and unidentified infections of the brain (p = 0.000). No significant difference was found (p = 1.000) when comparing viral and unidentified neuroinfection. The area under the receiver operating characteristic curve for serum PCT was 0.823 but could be increased to 0.929 when combining serum PCT and C-reactive protein (CRP). CONCLUSION: Serum PCT levels are significantly higher in patients with acute bacterial infections of the brain. As a stand-alone biomarker, its discriminatory power is not superior to the classical laboratory parameters in the cerebrospinal fluid and serum CRP. However, when combined with serum CRP, excellent discriminatory power is observed.

scholarly journals Invasion of the Brain and Chronic Central Nervous System Infection after Systemic Mycobacterium avium Complex Infection in Mice

2000 ◽  
Vol 68 (5) ◽  
pp. 2979-2984 ◽  
Author(s):  
Hsiu-Shan Wu ◽  
Peter Kolonoski ◽  
Yung Yee Chang ◽  
Luiz E. Bermudez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mycobacterium Avium ◽  
Central Nervous System Infection ◽  
Clinical Signs ◽  
Cns Infection ◽  
Low Grade ◽  
Granulomatous Lesions ◽  
Inflammatory Changes ◽  
The Brain

ABSTRACT Central nervous system (CNS) infections caused by nontuberculous mycobacteria have been described previously, especially in patients with AIDS. To investigate specific aspects of the pathogenesis of this entity, C57BL bg +/bg −mice were infected intravenously with Mycobacterium avium, and cultures of blood and brain as well as histopathology examination of brain tissue were carried out at several time points up to 6 months after infection. Low-grade inflammatory changes with small aggregates of lymphocytes and macrophages as well as perivascular cuffing were seen early in the infection. A small number of bacteria could be observed in the parenchyma of the choroid plexus. Six months after infection, numerous bacteria were present within the foamy macrophage of the granulomatous lesions along the ventricle and meninges. None of the mice developed clinical signs of meningitis or encephalitis or even died spontaneously during the period of observation. Use of CD18−/− knockout mice indicated that transport of the bacterium within neutrophils or monocytes into the brain is unlikely. Mild chronic CNS infection developed in the mice during sustained systemic M. avium infection, similar to what has been reported in most human cases.

scholarly journals Identification of Unique Hepatitis C Virus Quasispecies in the Central Nervous System and Comparative Analysis of Internal Translational Efficiency of Brain, Liver, and Serum Variants

2004 ◽  
Vol 78 (10) ◽  
pp. 5170-5183 ◽  
Author(s):  
Daniel M. Forton ◽  
Peter Karayiannis ◽  
Nadiya Mahmud ◽  
Simon D. Taylor-Robinson ◽  
Howard C. Thomas
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymph Node ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cns Infection ◽  
Translational Efficiency ◽  
Huh7 Cells ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Reports of cerebral dysfunction in chronic hepatitis C virus (HCV) infection have led to the suggestion that HCV may infect the central nervous system (CNS). We used reverse transcription-PCR, cloning, and sequencing to define quasispecies for the HCV internal ribosomal entry site (IRES) and hypervariable region 1 (HVR1) in autopsy-derived brain, liver, lymph node, and serum samples. There was evidence of tissue compartmentalization of sequences in the brain in two patients, with between 24 and 55% of brain-derived IRES sequences absent from the serum, and significant phylogenetic and phenetic clustering of the brain and lymph node HVR1 sequences. The IRES initiates cap-independent translation of the viral polyprotein. Two unique brain-derived IRES mutations (C204→A and G243→A), which have previously been associated with lymphoid replication and altered translational efficiency in cell culture, were found in one patient. We used a dicistronic reporter vector to test whether brain-derived variants showed altered IRES-mediated translational efficiency, which might favor CNS infection. The translational efficiencies of the brain-derived IRES sequences were generally reduced compared to those of the master serum and liver sequences in rabbit reticulocyte cell lysates and two human cell lines, HuH7 (liver) and CHME3 (microglial). The C204→A and G243→A mutations showed preserved translational efficiency in HuH7 cells but reduced efficiency in CHME3 cells. Our data provide evidence that the CNS is a site of HCV replication, consistent with the recent demonstration of negative-strand HCV RNA in brain, and suggest that IRES polymorphisms may be important as a viral strategy of reduced translation to favor latency in the CNS.

scholarly journals Evaluation of the Mtb72F Polyprotein Vaccine in a Rabbit Model of Tuberculous Meningitis

2006 ◽  
Vol 74 (4) ◽  
pp. 2392-2401 ◽  
Author(s):  
Liana Tsenova ◽  
Ryhor Harbacheuski ◽  
Andre L. Moreira ◽  
Evette Ellison ◽  
Wilfried Dalemans ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Weight Loss ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Mycobacterium Tuberculosis ◽  
Tuberculous Meningitis ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Cns Infection ◽  
The Brain

ABSTRACT Using a rabbit model of tuberculous meningitis, we evaluated the protective efficacy of vaccination with the recombinant polyprotein Mtb72F, which is formulated in two alternative adjuvants, AS02A and AS01B, and compared this to vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) alone or as a BCG prime/Mtb72F-boost regimen. Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS) challenge with Mycobacterium tuberculosis H37Rv to an extent comparable to that of vaccination with BCG. Similar accelerated clearances of bacilli from the cerebrospinal fluid, reduced leukocytosis, and less pathology of the brain and lungs were noted. Weight loss of infected rabbits was less extensive for Mtb72F+AS02A-vaccinated rabbits. In addition, protection against M. tuberculosis H37Rv CNS infection afforded by BCG/Mtb72F in a prime-boost strategy was similar to that by BCG alone. Interestingly, Mtb72F+AS01B induced better protection against leukocytosis and weight loss, suggesting that the polyprotein in this adjuvant may boost immunity without exacerbating inflammation in previously BCG-vaccinated individuals.

scholarly journals Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice

2018 ◽  
Vol 236 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Hannah M Eggink ◽  
Lauren L Tambyrajah ◽  
Rosa van den Berg ◽  
Isabel M Mol ◽  
Jose K van den Heuvel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Bile Acids ◽  
Fat Oxidation ◽  
Final Concentration ◽  
The Central Nervous System ◽  
The Brain

Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracerebroventricular (i.c.v.) administration of taurolithocholate (tLCA), a strong TGR5 agonist, and GW4064, a synthetic FXR agonist, on energy metabolism. We determined the effects of chronic i.c.v. infusion of tLCA, GW4064, or vehicle on energy expenditure, body weight and composition as well as tissue specific fatty acid uptake in mice equipped with osmotic minipumps. We found that i.c.v. administration of tLCA (final concentration in cerebrospinal fluid: 1 μM) increased fat oxidation (tLCA group: 0.083 ± 0.006 vs control group: 0.036 ± 0.023 kcal/h, F = 5.46, P = 0.04) and decreased fat mass (after 9 days of tLCA infusion: 1.35 ± 0.13 vs controls: 1.96 ± 0.23 g, P = 0.03). These changes were associated with enhanced uptake of triglyceride-derived fatty acids by brown adipose tissue and with browning of subcutaneous white adipose tissue. I.c.v. administration of GW4064 (final concentration in cerebrospinal fluid: 10 μM) did not affect energy metabolism, body composition nor bile acid levels, negating a role of FXR in the central nervous system in metabolic control. In conclusion, bile acids such as tLCA may exert metabolic effects on fat metabolism via the brain.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

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