EVIDENCE FOR EARLY BLOOD-BRAIN-BARRIER BREAKDOWN IN EXPERIMENTAL THIAMINE-DEFICIENCY IN THE MOUSE

In order to assess the involvement of blood-brain barrier (BBB) breakd own in the pathogenesis of thiamine deficiency encephalopathy, autolog ous albumin immunohistochemistry was performed in mice which were rend ered thiamine-deficient by pyrithiamine, a BBB-permeant antagonist of thiamine. In the presymptomatic animals until day 8 of the treatment, histological lesions were not detected by H&E staining. However, local ized staining of albumin was evident, suggesting an extravascular leak age of the endogenous intravascular protein. On day 10 of thiamine def iciency, when neurological signs appeared, both histological lesions a nd massive albumin extravasation were demonstrated in ail the animals. The BBB breakdown was only occasionally observed in the brains of mic e treated with oxythiamine, a BBB-impermeant antagonist or in control animals. These results suggest that BBB breakdown is not only a phenom enon secondary to tissue destruction, but it is more directly involved in the pathogenesis of thiamine deficiency encephalopathy.