Neuronal apoptosis does not play an important role in human rabies encephalitis

Jackson, Alan C.; Randle, Elizabeth; Lawrance, Gail; Rossiter, John P.

doi:10.1080/13550280802216502

Cited by 61 publications

(51 citation statements)

References 22 publications

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“…En general, la apoptosis no parece ser un fenómeno importante en la fisiopatología de la rabia (30,31). Sin embargo, es posible que el virus genere alteraciones funcionales en las neuronas que expresan esta proteína.…”

Section: Efecto De La Infección Viral Sobre La Expresión De Cb Y Pvunclassified

Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones

Monroy-Gómez

Torres‐Fernández

2013

biomedica

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Contribución de los autores:Jeison Monroy-Gómez: planeación y diseño del trabajo; desarrollo de los experimentos, análisis de resultados, elaboración de borrador del manuscrito y revisión final. Orlando Torres-Fernández: idea, planeación, diseño y dirección general del trabajo; análisis de resultados, revisión y versión final del manuscrito. ARTÍCULO ORIGINAL Biomédica 2013;33:564-73 doi: http://dx.doi.org/10.7705/biomedica.v33i4.1552 Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones Introducción. Aunque se trata de una enfermedad infecciosa del sistema nervioso, poco se conoce sobre los mecanismos patogénicos de la infección con el virus de la rabia. En particular, son escasos los estudios sobre su histopatología en la médula espinal. Objetivo. Estudiar la distribución de las proteínas calbindina y parvoalbúmina, en la médula espinal de ratones y evaluar el efecto de la infección con el virus de la rabia sobre su expresión. Materiales y métodos. Se inocularon ratones con virus de la rabia, por vía intracerebral o intramuscular, y se extrajo la médula espinal para hacer cortes transversales, los cuales se sometieron a tratamiento inmunohistoquímico con anticuerpos monoclonales para revelar la presencia de las dos proteínas en ratones normales y en animales infectados. Se llevó a cabo el análisis cualitativo y cuantitativo de la inmunorreacción de las dos proteínas. Resultados. Las proteínas calbindina y parvoalbúmina se distribuyeron de manera diferencial en las láminas de Rexed. La infección con el virus de la rabia produjo una disminución en la expresión de calbindina. Por el contrario, la infección provocó un incremento en la expresión de parvoalbúmina. El efecto de la rabia sobre las dos proteínas fue similar al comparar las dos vías de inoculación. Conclusión. El efecto diferencial de la infección con el virus de la rabia sobre calbindina y parvoalbúmina en la médula espinal de ratones, es similar al reportado anteriormente para áreas encefálicas. Esto sugiere uniformidad en su respuesta a la infección en todo el sistema nervioso central y es un aporte importante para el conocimiento de la patogénesis de la rabia.Palabras clave: virus de la rabia, médula espinal, neuronas, ratones, inmunohistoquímica. doi: http://dx.doi.org/10.7705/biomedica.v33i4.1552 Calbindin and parvalbumin distribution in spinal cord of normal and rabies-infected miceIntroduction: Rabies is a fatal infectious disease of the nervous system; however, the knowledge about the pathogenic neural mechanisms in rabies is scarce. In addition, there are few studies of rabies pathology of the spinal cord. Objective: To study the distribution of calcium binding proteins calbindin and parvalbumin and assessing the effect of rabies virus infection on their expression in the spinal cord of mice. Materiales y methods: Mice were inoculated with rabies virus, by intracerebral or intramuscular route. The spinal cord was extracted to perform some crosscuts which were treated ...

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Section: Efecto De La Infección Viral Sobre La Expresión De Cb Y Pvunclassified

Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones

Monroy-Gómez

Torres‐Fernández

2013

biomedica

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“…42,45 Contrary to previous reports, 46 we have recently provided strong evidence that neuronal apoptosis does not play an important role in human rabies. 47 Hence, in rabies virus infection there are complex mechanisms involved in the death or survival of neurons both in vitro and in animal models using different viral strains and routes of inoculation, but neuronal cell death is not prominent in natural rabies. Neuronal apoptosis is a host mechanism employed to limit viral spread and does not serve a fundamental role in the pathogenesis of rabies.…”

Section: Mechanisms For Neuronal Dysfunction and Deathmentioning

confidence: 99%

Update on rabies

Jackson¹

2011

RRTM

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Human rabies is almost invariably fatal, and globally it remains an important public health problem. Our knowledge of rabies pathogenesis has been learned mainly from studies performed in experimental animal models, and a number of unresolved issues remain. In contrast with the neural pathway of spread, there is still no credible evidence that hematogenous spread of rabies virus to the central nervous system plays a significant role in rabies pathogenesis. Although neuronal dysfunction has been thought to explain the neurological disease in rabies, recent evidence indicates that structural changes involving neuronal processes may explain the severe clinical disease and fatal outcome. Endemic dog rabies results in an ongoing risk to humans in many resource-limited and resource-poor countries, whereas rabies in wildlife is important in North America and Europe. In human cases in North America, transmission from bats is most common, but there is usually no history of a bat bite and there may be no history of contact with bats. Physicians may not recognize typical features of rabies in North America and Europe. Laboratory diagnostic evaluation for rabies includes rabies serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Methods of postexposure rabies prophylaxis, including wound cleansing and administration of rabies vaccine and human rabies immune globulin, are highly effective after recognized exposure. Although there have been rare survivors of human rabies, no effective therapy is presently available. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (known as the "Milwaukee protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. New therapeutic approaches for human rabies need to be developed. A better understanding of basic mechanisms involved in rabies pathogenesis may be helpful in the development of potential new therapies for the future.

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“…Street-virusinfected suckling mice revealed TUNEL labelling of occasional microglial cells in the cerebral cortex and brain stem (21). On the other hand, evaluation of morphological features of neuronal apoptosis in postmortem brain tissue from human rabies victims collected from different countries suggested that neuronal apoptosis does not play an important role in human rabies encephalitis (11).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis in natural rabies virus infection in dogs

Vural

Bozkurt

Ozkara

et al. 2016

Journal of Veterinary Research

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Introduction: In the present study apoptosis was investigated in the cornu ammonis and cerebellum of 10 dogs naturally infected with rabies virus. Diagnosis of rabies was based on the results of fluorescent antibody staining and experimental inoculation. Material and Methods: The paraffin tissue sections were stained with haematoxylin and eosin, avidin-biotin complex peroxidase (ABC-P), and terminal deoxynucleotidyl transferase biotin-dUTP nick end-labelling (TUNEL) methods. Results: Histopathological examination revealed encephalomyelitis of varying severity and the presence of Negri bodies. Dense rabies antigens were determined in the motor neurons with ABC-P method. On the other hand, Bcl-2 protein and Bax protein gave positive reaction in seven and five cases, respectively. TUNEL staining demonstrated very marked apoptotic changes in the nuclei of neurons localised deep in the substantia alba of the cerebellum. Similar changes were also determined in perivascular mononuclear cells and glia cells within the substantia alba. No apoptopic changes were found in the motor neurons of the cornu ammonis. Conclusion: The absence of apoptotic changes in the neurons was considered to be the consequence of the necrotic changes that developed in these neurons.

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Neuronal apoptosis does not play an important role in human rabies encephalitis

Cited by 61 publications

References 22 publications

Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones

Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones

Update on rabies

Apoptosis in natural rabies virus infection in dogs

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