Early microglial response in experimental thiamine deficiency: an immunohistochemical analysis.
Early glial changes have consistently been reported in experimental thiamine 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., Philadelphia, 1989.). However, the precise nature of these changes and their relationship to the phenomenon of selective neuronal cell loss in TD has not been elucidated. In the present studies, antibodies against GFAP and ED1 were used to evaluate astrocytic and microglial/macrophagic changes respectively in adjacent sections of the brains of thiamine-deficient rats at various stages (n = 6 per stage) during the progression of encephalopathy. Additionally, the integrity of the blood-brain barrier at the same stages was assessed using IgG immunohistochemistry. Counts of immuno-positive cells revealed significant increases of ED1-immunostaining in the inferior olive, medial geniculate nucleus, and medial thalamic nuclei on day 8 of the treatment paradigm, prior to any evidence of increased IgG immunostaining or significant neuronal cell loss. ED1 immunostaining increased over time, resulting in 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 increased GFAP-immunostaining consistent with reactive gliosis. Early microglial activation leading to the release of cytotoxic substances including reactive oxygen species, glutamate and cytokines appears to be the initial cellular response to TD and could be responsible for the focal neuronal loss characteristic of this disorder.
Todd
K G
KG
Neuroscience Research Unit, Hôpital St-Luc (University of Montreal), Canada.
Butterworth
R F
RF
D000818:Animals; D001041:Aphasia, Wernicke / Q000473:pathology; D015415:Biomarkers; D016923:Cell Death / Q000187:drug effects; D004032:Diet; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000473:pathology*
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G