FOUND HEREImmune 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 tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery 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. Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP. Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance. Immunohistochemistry revealed transforming growth factor β1 production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor β1 levels were equivalent in both groups. Corticosterone levels 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 response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome.
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Background: Ischemic injury to the central nervous system causes cellular activation and disintegration, leading to release of cell-type–specific proteins into the cerebrospinal fluid (CSF). We investigated CSF concentrations of myelin basic protein (MBP), glial fibrillary astrocytic protein (GFAP), the calcium-binding protein S100B, and neuron-specific enolase (NSE) in acute ischemic stroke patients and their relation to initial stroke severity, stroke location, and long-term stroke outcome.
Methods: CSF concentrations of MBP, GFAP, S100B, and NSE were assessed in 89 stroke patients on admission (mean 8.7 h after stroke onset) and in 35 controls. We evaluated the relation between CSF concentrations and (a) stroke severity (NIH Stroke Scale [NIHSS] score on admission, infarct volume), (b) stroke location, and (c) stroke outcome (modified Rankin Scale [mRS] score at month 3).
Results: MBP concentration was significantly higher in subcortical than in cortical infarcts (median MBP, 1.18 vs 0.66 µg/L, P < 0.001). GFAP and S100B concentrations correlated with the NIHSS score on admission (GFAP, R = 0.35, P = 0.001; S100B, R = 0.29, P = 0.006), infarct volume (GFAP, R = 0.34, P = 0.001; S100B, R = 0.28, P = 0.008), and mRS score at month 3 (R = 0.42, P < 0.001 and R = 0.28, P = 0.007). Concentrations of NSE did not correlate with stroke characteristics.
Conclusions: MBP, GFAP, S100B, and NSE display relevant differences in cellular and subcellular origins, which are reflected in their relation to stroke characteristics. MBP is a marker for infarct location. GFAP and S100B correlate with stroke severity and outcome.
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