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Experimental Reovirus-Induced Acute Flaccid Paralysis and Spinal Motor Neuron Cell Death
- Publication Year :
- 2008
-
Abstract
- Acute flaccid paralysis (AFP) describes the loss of motor function in 1 or more limbs commonly associated with viral infection and destruction of motor neurons in the anterior horns of the spinal cord. Therapy is limited, and the development of effective treatments is hampered by a lack of experimental models. Reovirus infection of neonatal mice provides a model for the study of CNS viral infection pathogenesis. Injection of the Reovirus serot Type 3 strains Abney (T3A) or Dearing (T3D) into the hindlimb of 1-day-old mice resulted in the development of AFP in more than 90% of infected mice. Acute flaccid paralysis began in the ipsilateral hindlimb at 8 to 10 days postinfection and progressed to paraplegia 24 hours later. Paralysis correlated with injury, neuron loss, and spread of viral antigen first to the ipsilateral and then to the contralateral anterior horns. As demonstrated by the activation of caspase 3 and its colocalization with viral antigen in the anterior horn and concomitant cleavage of poly-(adenosine diphosphate-ribose) polymerase, AFP was associated with apoptosis. Calpain activity and inducible nitric oxide synthase expression were both elevated in the spinal cords of paralyzed animals. This study represents the first detailed characterization of a novel and highly efficient experimental model of virus-induced AFP that will facilitate evaluation of therapeutic strategies targeting virus-induced paralysis.
- Subjects :
- Flaccid paralysis
Nitric Oxide Synthase Type II
Apoptosis
Hindlimb
Article
Spinal Cord Diseases
Pathology and Forensic Medicine
Pathogenesis
Cellular and Molecular Neuroscience
Mice
medicine
Paralysis
Animals
Motor Neuron Disease
Antigens, Viral
Mammalian orthoreovirus 3
Cells, Cultured
Motor Neurons
biology
Calpain
Caspase 3
General Medicine
Motor neuron
Spinal cord
medicine.disease
Reoviridae Infections
Disease Models, Animal
medicine.anatomical_structure
Neurology
Animals, Newborn
Immunology
Nerve Degeneration
biology.protein
Disease Progression
Neurology (clinical)
medicine.symptom
Poly(ADP-ribose) Polymerases
Paraplegia
Biomarkers
West Nile Fever
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b07e8d9ca3a2b68dc32771fda88aca3a