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) breakdown in the pathogenesis of thiamine deficiency encephalopathy, autologous albumin immunohistochemistry was performed in mice which were rendered 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, localized straining of albumin was evident, suggesting an extravascular leakage of the endogenous intravascular protein. On day 10 of thiamine deficiency, when neurological signs appeared, both histological lesions and massive albumin extravasation were demonstrated in all the animals. The BBB breakdown was only occasionally observed in the brains of mice treated with oxythiamine, a BBB-impermeant antagonist or in control animals. These results suggest that BBB breakdown is not only a phenomenon secondary to tissue destruction, but it is more directly involved in the pathogenesis of thiamine deficiency encephalopathy.