IMMUNOLOGICAL-TOLERANCE TO MYELIN BASIC-PROTEIN DECREASES STROKE SIZEAFTER TRANSIENT FOCAL CEREBRAL-ISCHEMIA

Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tole rance to myelin basic protein (MBP). Lewis rats were fed low-dose bovi ne MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral a rtery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals, Toleran ce to MBP was confirmed in vivo by a decrease in delayed-type hypersen sitivity to MBP, Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance, Immunohistochemistr y revealed transforming growth factor pi production by T cells in the brains of tolerized but not control animals. Systemic transforming gro wth factor pi levels were equivalent in both groups. Corticosterone le vels 24 h after surgery were elevated in all sham operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune re sponse decreases infarct size after focal cerebral ischemia and that s ensitization to the same antigen may actually worsen outcome.