Early microglial response in experimental thiamine deficiency: An immunohistochemical analysis

Early glial changes have consistently been reported in experimental thiamin e deficiency (TD) (Tellez and Terry, Am. J. Pathol. 52:777-794, 1968.) and in Wernicke Encephalopathy in humans (Victor et al., F.A. Davis Co., Philad elphia, 1989.). However, the precise nature of these changes and their rela tionship to the phenomenon of selective neuronal cell loss in TD has not be en elucidated. In the present studies, antibodies against GFAP and ED1 were used to evaluate astrocytic and microglial/ macrophagic changes respective ly in adjacent sections of the brains of thiamine-deficient rats at various stages (n = 6 per stage) during the progression of encephalopathy. Additio nally, the integrity of the blood-brain barrier at the same stages was asse ssed using IgG immunohistochemistry. Counts of immune-positive cells reveal ed significant increases of ED1-immunostaining in the inferior olive, media l geniculate nucleus, and medial thalamic nuclei on day 8 of the treatment paradigm, prior to any evidence of increased IgG immunostaining or signific ant neuronal cell loss. ED1 immunostaining increased over time, resulting i n intense staining by the loss of righting reflex stage (day 13-15). Focal increases of IgG-immunoreactivity in inferior olive, medial dorsal thalamus , and medial geniculate nucleus were observed on day 10, followed by increa sed GFAP-immunostaining consistent with reactive gliosis. Early microglial activation leading to the release of cytotoxic substances including reactiv e oxygen species, glutamate and cytokines appears to be the initial cellula r response to TD and could be responsible for the focal neuronal loss chara cteristic of this disorder. GLIA 25:190-198, 1999. (C) 1999 Wiley-Liss, Inc .