Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy

A large increase in the number and percentage of degranulating mast cells w as observed within thalamus of rats after 6-7 days of thiamine deficiency ( TD). No mast cells were detected in the inferior olivary and lateral vestib ular nuclei, which are also severely damaged by TD. After 11-12 days of TD, the number of ED2 immunopositive macrophages increased in thalamus. In the brainstem nuclei, an increase in the number of macrophages occurred much e arlier in treatment (i.e. day 6). An increase in GFAP-positive astrocytes w ithin thalamus occurred after the changes in mast cells and prior to the in crease in macrophages. In brainstem, reactive astrocytes appeared along wit h the increase in macrophages. These data suggest that mast cell degranulat ion is a very early response induced by TD, and the resultant release of cy tokines and other chemical mediators may play critical roles in both the ea rly vascular damage and eventual tissue destruction within thalamus, but no t within brainstem. These results also suggest that macrophages and reactiv e astrocytes may play more direct roles in the pathogenesis of brainstem le sions.