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| Tracey Newman |
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CNS Inflammation Group, Univ of Southampton, UK
e-mail: tan@soton.ac.uk |
Poster Presentation: |
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| AXONAL INJURY IN AN MRI-SILENT INFLAMMATORY LESION. |
| TA Newman, ST Woolley, NR Sibson, DC Anthony and VH PERRY | |
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CNS Inflammation Group, Univ of Southampton, UK |
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| Neuropathologically Multiple sclerosis (MS) is characterised by the presence of inflammatory infiltrates of T-cells and macrophages. Areas of demyelination have long been regarded as the hallmarks of MS lesions, however, recent efforts have also focused on axonal injury which has been demonstrated to occur in these lesions. In order to investigate this component of the lesion further we have studied a model of a focal immune lesion in the rat brain. An intrastriatal injection of heat killed Bacillus Calmette Guerin (BCG), followed by a peripheral challenge with BCG in adjuvant results in a delayed type hypersensitivity (DTH) lesion centred on the initial injection site of the BCG. The lesion is composed mainly of T-cells and macrophages. Immunohistological examination of these lesions reveals evidence of axon injury as demonstrated by the presence of APP end bulbs around the lesions. MRI investigation of animals with DTH lesions shows that the early lesion has a period of blood brain barrier breakdown seen as a region of gadolinium enhancement on a T1 weighted MRI image. However, at later time points the region of gadolinium enhancement is no longer evident. An investigation of axon injury in a traumatic injury model has shown that the majority of APP+ve end bulbs are no longer evident 7 days after the injury. Even after a period of one month there is still clear evidence of APP+ve end bulbs, showing that there is ongoing axonal injury in these lesions behind an intact blood brain barrier. There is now evidence that the use of MRI as a prognostic indicator in MS is not reliable. Results from this study suggest that this is because axon injury is continuing to accumulate in non-gadolinium enhancing lesions. Axon injury is now recognised as the main predictor of neurological disability in MS. There is now also evidence that normal appearing white matter is also affected by the pathological processes occurring in the disease. This suggests that rather than the disease being quiescent during periods of remission, in relapsing-remitting disease, that ongoing injury continues to accumulate and may even in part explain the transition from relapsing-remitting to secondary progressive disease. Therapies targeted at preventing the axon injury as early as possible are clearly needed.
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