FOCAL BRAIN-DAMAGE ENHANCES EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN BRAIN AND SPINAL-CORD

The immunological basis of multiple sclerosis (MS) is well recognized but the factors inducing MS lesions are unclear. In this study, we tes t the hypothesis that focal brain injury, inflicted during the pre-cli nical stages of experimental allergic encephalomyelitis (EAE), will en hance the severity of immunological damage in the cerebral hemispheres and spinal cord. Acute EAE was induced in 30 Lewis rats by the inject ion of guinea pig spinal cord homogenate in complete Freund's adjuvant . A cryolesion to the surface of the left cerebral hemisphere was indu ced at 3 days (n=6) or 8 days (n=10) postinoculation (p.i.) and animal s were killed at 15 days p.i. Control animals were EAE only (n=9), cry olesion only (n=4), EAE and sham cryolesion (n=5) and normal animals ( n=3). Brain and spinal cord were stained by immunocytochemistry using W3/13 (T-lymphocytes) OX6 (MHC Class II) and GFAP (astrocytes) antibod ies. The results showed a 2-fold increase in the number of EAE lesions in the brain with significant and widespread increase of MHC Class II antigen expression by microglia, in the cryolesion EAE 8 days p.i whe n compared with EAE only animals. The pattern of enhancement suggests that it is due to (i) local spread of tissue or serum factors from the cryolesion; (ii) neural factors affecting remote regions of the CNS; (iii) stimulation of the immune system which may occur due to products of brain injury draining to regional cervical lymph nodes. Investigat ion of the mechanisms involved may prove fruitful in establishing fact ors which initiate, aggravate or ameliorate brain damage in multiple s clerosis.