scholarly journals Macrophage Infiltration, but Not Apoptosis, Is Correlated with Immune-Mediated Demyelination following Murine Infection with a Neurotropic Coronavirus

1999 ◽  
Vol 73 (10) ◽  
pp. 8771-8780 ◽  
Author(s):  
Gregory F. Wu ◽  
Stanley Perlman

ABSTRACT Mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis that is in large part immune mediated. Potential mechanisms of immune activity were assessed using an adoptive transfer system. Mice deficient in recombinase-activating gene function (RAG1−/−), defective in B- and T-cell maturation, become persistently infected with MHV but do not develop demyelination. Adoptive transfer of splenocytes from mice immunized to MHV into RAG1−/− mice infected with an attenuated strain of the virus results in the rapid and progressive development of demyelination. Most striking, adoptive transfer resulted, within 5 to 6 days, in extensive recruitment of activated macrophages/microglia to sites of demyelination within the spinal cord. Clearance of virus antigen occurred preferentially from the gray matter of the spinal cord. Apoptotic cells were identified in both the gray and white matter of the central nervous system (CNS) from RAG1−/− mice before and after adoptive transfer, with a moderate increase in number, but not distribution, of apoptotic cells following the development of demyelination. These results suggest that apoptosis following MHV-JHM infection of the murine CNS is not sufficient to cause demyelination. These results, showing that macrophage recruitment and myelin destruction occur rapidly after immune reconstitution of RAG−/− mice, suggest that this will be a useful system for investigating MHV-induced demyelination.

1958 ◽  
Vol 192 (3) ◽  
pp. 447-452 ◽  
Author(s):  
Sadayuki F. Takagi ◽  
Yutaka Oomura

The effect of nicotine on synaptic transmission in the frog and cat spinal cord was studied. Both a regular wick electrode and a microelectrode of the Ling-Gerard type were used. The reflex activity of the bullfrog spinal cord is facilitated by 0.01% nicotine solution, but is depressed and abolished by 0.1% solution. In the cat, intravenous administration of 150 mg/kg fails to block reflex activity, but topical application does block. The intracellular potential, of both frog and cat motoneurones, shows no change in the synaptic potential after application of the drug, but the spike appears after a shorter synaptic delay and one or more additional spikes appear. When the synaptic delay becomes sufficiently short, however, all spikes suddenly disappear, leaving the still unchanged synaptic potential. Occasionally the synaptic delay is again increased just before the spike potentials disappear. The excitability of a frog motoneurone was measured, by a recording microelectrode, before and after nicotine application. The drug first increased and then decreases excitability. Epinephrine can restore a reflex discharge depressed or abolished by nicotine. It is concluded that high concentrations of nicotine block synaptic transmission in the central nervous system, acting on the cell body but not on the synaptic potential.


2000 ◽  
Vol 74 (16) ◽  
pp. 7683-7686 ◽  
Author(s):  
Gregory F. Wu ◽  
Lecia Pewe ◽  
Stanley Perlman

ABSTRACT Demyelination induced by mouse hepatitis virus (MHV), strain JHM, is in large part immune mediated, but little is known about the mechanisms involved in this process. Previous results suggest that inducible nitric oxide synthase (NOS2) contributes transiently to MHV-induced demyelination. Herein, we show that equivalent amounts of demyelination were evident at day 12 after MHV infection in mice genetically deficient in NOS2 (NOS2−/−) and in C57BL/6 mice. Furthermore, using an established adoptive transfer model and pharmacological inhibitors of NOS2 function, we could demonstrate no effect on MHV-induced demyelination. These results indicate that NOS2 function is not required for demyelination in mice infected with MHV.


2005 ◽  
Vol 79 (6) ◽  
pp. 3370-3381 ◽  
Author(s):  
Katherine C. MacNamara ◽  
Ming Ming Chua ◽  
Peter T. Nelson ◽  
Hao Shen ◽  
Susan R. Weiss

ABSTRACT CD8+ T cells are important for clearance of neurotropic mouse hepatitis virus (MHV) strain A59, although their possible role in A59-induced demyelination is not well understood. We developed an adoptive-transfer model to more clearly elucidate the role of virus-specific CD8+ T cells during the acute and chronic phases of infection with A59 that is described as follows. C57BL/6 mice were infected with a recombinant A59 virus expressing the gp33 epitope, an H-2Db-restricted CD8+ T-cell epitope encoded in the glycoprotein of lymphocytic choriomeningitis virus, as a fusion with the enhanced green fluorescent protein (RA59-gfp/gp33). P14 splenocytes (transgenic for a T-cell receptor specific for the gp33 epitope) were transferred at different times pre- and postinfection (p.i.). Adoptive transfer of P14 splenocytes 1 day prior to infection with RA59-gfp/gp33, but not control virus lacking the gp33 epitope, RA59-gfp, reduced weight loss and viral replication and spread in the brain and to the spinal cord. Furthermore, demyelination was significantly reduced compared to that in nonrecipients. However, when P14 cells were transferred on day 3 or 5 p.i., no difference in acute or chronic disease was observed compared to that in nonrecipients. Protection in mice receiving P14 splenocytes prior to infection correlated with a robust gp33-specific immune response that was not observed in mice receiving the later transfers. Thus, an early robust CD8+ T-cell response was necessary to reduce virus replication and spread, specifically to the spinal cord, which protected against demyelination in the chronic phase of the disease.


2011 ◽  
Vol 106 (3) ◽  
pp. 1363-1378 ◽  
Author(s):  
Jinsook Roh ◽  
Vincent C. K. Cheung ◽  
Emilio Bizzi

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas.


2018 ◽  
Vol 89 (10) ◽  
pp. A19.3-A19
Author(s):  
White Daniel ◽  
Patel Markand ◽  
Muhammad Wasim ◽  
Hayton Tom ◽  
Ramalingam Satheesh ◽  
...  

BackgroundAutoimmune Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or subacute onset of cognitive impairment, seizures, encephalopathy, meningeal symptoms to more complex forms of encephalomyelitis.Materials and MethodsWe present a radiological review of two cases which were recently diagnosed in our institution. They presented with fever, meningoencephalitis and bilateral papilloedema. CSF antibody analysis (GFAPα-IgG) from Mayo Clinic confirmed the diagnosis of GFAP in both cases.ResultsThe typical radiological findings in both of the cases were a radial pattern of enhancement in brain and longitudinally extensive myelitic lesions in the spinal cord. The first patient improved with immunosupression treatment. The second patient had a significantly more severe clinical presentation with drug-refractory progression, who later died.ConclusionPatients presenting with subacute onset of cognitive impairment, meningoencephalomyelitis and papilloedema should raise the suspicion of autoimmune GFAP astrocytopathy. Though it is a relatively new disease entity, the radial pattern of enhancement and long spinal cord lesions on imaging are striking and CSF and serum antibodies are highly specific.


2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell

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.


2013 ◽  
Vol 41 (01) ◽  
pp. 63-66
Author(s):  
D. Schaudien ◽  
C. Flieshardt ◽  
I. Moser ◽  
H. Hotzel ◽  
A. Tipold ◽  
...  

SummaryGranulomatous myelitis due to infection with Mycobacterium avium was diagnosed in a 4-year-old male neutered European mink (Mustela lutreola). The causative agent was detected by an acid-fast stain and further characterized by polymerase chain reaction and DNA sequencing of the PCR product. A thorough histological evaluation of the remaining organs revealed no granulomatous lesions or detectable acid-fast organisms. Although minks are generally highly susceptible for mycobacteria, localised infections, especially of the central nervous system, are unusual and may represent an atypical chronic form of the disease.


2017 ◽  
Vol 4 (2) ◽  
pp. 14
Author(s):  
Putri Megasari

Hepatitis has become a health problem in the world. The hepatitis virus infected many people. According to the teacher of MTsN 02 Bondowoso more than 20 students have hepatitis A viral infection. The purpose of this research was to know the differences of students' knowledge about hepatitis A before and after counseling in MTsN 02 Bondowoso 2015. This study used pre-experimental (pre-post test design). This study used stratified random sampling technique, 127 students from 270 sample involved this research,and 143 students was excluded. We used questionnaires to collect data. The results showed that the mean value of the students 'knowledge about hepatitis A before counseling in MTsN 02 Bondowoso 2015 was 83.96 with the lowest value of 37.5 and the highest value was 100. The mean value of the students' knowledge about hepatitis A after counseling in MTsN 02 Bondowoso 2015 was 93.21 with the lowest value waf 62.5 and the highest value was 100. Paired t test showed that t (-9.07) > t table (1.98), the null hypothesis (H0) was rejected. There was a difference between students' knowledge about hepatitis A before and after counseling in MTsN 02 Bondowoso 2015. This study showed that routine counseling by healthcare provider was important to prevent hepatitis A infection.; Keywords: counseling, knowledge of students, hepatitis


1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


1963 ◽  
Vol 42 (3) ◽  
pp. 437-452 ◽  
Author(s):  
H. Daweke

Using the method of glucose-1-14C oxydation to 14CO2 on the rat epididymal adipose tissue, the insulin-like activities (ILA) in the serum have been compared before and after oral loading with glucose in normal subjects, in maturity-onset diabetics and in insulin-requiring diabetics. In maturity-onset diabetics mean fasting values were found to be 30% below normal while in insulin-requiring diabetics they were 85% above normal. In normal subjects there was observed, 30 minutes after glucose loading, a moderate increase in blood sugar together with an increase of ILA of 222% above the starting value; in maturity-onset diabetics the increase in ILA was only 106% while the blood sugar was markedly increased. After glucose loading in maturity-onset diabetics, the total amount of insulin detected during the period of the experiment was, on the average, only 45% of that found in normal subjects. In insulin requiring diabetics there was no increase but, on the contrary, a steady decrease of the ILA values, while the blood sugar excessively increased. In general ILA values were higher than those in maturity-onset diabetics. No difference in response was found between maturity-onset diabetics treated with diet alone and those treated with diet and oral hypoglycaemic drugs. In contrast to the absolute ILA values, the index of insulin reserve, is of value in assessing the functional capacity of the pancreas. This index decreases progressively with the severity of the disease and reaches a maximum of 54% of the normal in maturity-onset diabetics, which can satisfactorily be explained by pancreas insufficiency. Only in some cases of insulin-requiring diabetics was an insulin reserve still detectable. The biological inactivity of the insulin circulating in the blood can be deduced from the increased ILA-values, as compared with those found in maturity-onset diabetics. Obviously some of this insulin can be released by the addition of glucose. It is likely that, in addition to pancreatic insufficiency, insulin-binding or insulin-inactivating antibodies play a part in the pathogenesis of insulin-requiring diabetes.


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