Focal brain damage and the enhancement of experimental allergic encephalomyelitis : its relevance to multiple sclerosis

Phillips, Marian Jean (1994) Focal brain damage and the enhancement of experimental allergic encephalomyelitis : its relevance to multiple sclerosis. University of Southampton, Doctoral Thesis.

Abstract

In this thesis the following hypotheses are tested: Firstly, focal brain damage enhances the severity of immunological damage in the cerebral hemispheres and spinal cord, secondly, drainage of brain-derived proteins and lipids via the lymphatic drainage pathways to the deep cervical lymph nodes is involved in this enhancement, and thirdly, microglia activated in cryolesion enhanced-EAE exhibit heterogeneity in morphology, function and pattern of involution.

The hypotheses are based on the following observations: a) Focal brain damage to the rat brain results in the rapid, widespread upregulation of perivascular cells, and b) interstitial fluid and possibly inflammatory cells drain via well defined lymphatic pathways to the deep cervical lymph nodes.

The results in this thesis show that: 1) Focal brain damage causes widespread enhancement of EAE, characterized by a significant increase in both the number of perivascular lymphocytic cuffs (p<0.01), and MHC II antigen expression on microglia (p<0.05) in the brain and spinal cord. 2) Morphological heterogeneity of microglia falls into 3 categories, a) around the cryolesion, b) in areas of lymphocyte infiltration, c) associated with neurons. This suggests that both the local spread of factors from the cryolesion, and neural mechanisms play a role in both the local and remote enhancement of EAE. 3) Lymphadenectomy reduces, but does not fully abolish, the cryolesion enhancement of EAE; this emphasises the role of lymphatic drainage of the brain and cervical lymph-nodes in the immunological attack on the CNS.

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