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Ultrastructural observations of spinal cord lesions and blood-brain barrier changes in scrapie-infected mice
Abstract:
Spinal cord samples from IM or VM mice injected intracerebrally with the 87V scrapie agent were examined ultrastructurally at the clinical stage of disease for changes in blood vessel permeability and for pathological alterations. In several animals, (3 of 16), massive changes were noted in the cervical spinal cords in the subependymal area of the cortical gray matter immediately surrounding the central canal including ependymal cell changes, the presence of amyloid plaque in close association with microglial cells, extensive neuropil vacuolation, the appearance of reactive astrocytes, degenerating neurites and vacuolated neurons. In those regions showing structural damage, localized increased permeability to horseradish peroxidase across the blood-brain barrier was noticed along with the appearance of numerous vesiculo-canalicular profiles in micro-blood vessel endothelial cells with extravasation of the tracer to the neuropil. Some damaged neurons appeared flooded with this tracer. These changes were not observed in either the thoracic or lumbar spinal cord regions. The occurrence of pathological changes in the spinal cords of a small percentage of intracerebrally injected mice was probably due to a high concentration of the scrapie agent which localized in the cervical spinal cord, presumably after entering the spinal fluid via the lateral ventricle at the time of injection.
Insights
Ultrastructural examination revealed significant blood-brain barrier disruptions and pathological changes in the cervical spinal cords of mice infected with the 87V scrapie agent. These alterations, including amyloid plaques and neuronal damage, were localized to the cervical region.
Area of Science:
- Neuroscience
- Pathology
- Prion Diseases
Background:
- Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system.
- Understanding the pathogenesis of prion diseases, like scrapie, is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate ultrastructural changes in the spinal cord of mice infected with the 87V scrapie agent.
- To examine blood-brain barrier permeability and pathological alterations in the spinal cord at the clinical stage of scrapie.
Main Methods:
- Ultrastructural examination of cervical, thoracic, and lumbar spinal cord samples from mice infected with the 87V scrapie agent.
- Horseradish peroxidase tracer was used to assess blood-brain barrier permeability.
Main Results:
- Three out of 16 mice exhibited massive pathological changes in the cervical spinal cord, including ependymal cell changes, amyloid plaques, neuropil vacuolation, reactive astrocytes, and neuronal damage.
- Increased blood-brain barrier permeability to horseradish peroxidase was observed in affected cervical spinal cord regions.
- These pathological changes and blood-brain barrier disruptions were localized to the cervical spinal cord and not found in thoracic or lumbar regions.
Conclusions:
- The 87V scrapie agent can induce significant ultrastructural pathology and blood-brain barrier breakdown in the cervical spinal cord.
- The localized nature of these changes suggests a potential concentration of the scrapie agent in the cervical spinal cord following intracerebral injection.
- Further research is needed to elucidate the precise mechanisms of prion neuroinvasion and neurodegeneration in the spinal cord.