Quantitative autoradiography using selective radioligands for central and peripheral-type benzodiazepine receptors in experimental Wernicke's encephalopathy: implications for positron emission tomography imaging.

Abstract

Wernicke's encephalopathy (WE) is difficult to diagnose during life, with up to 80% of cases being missed by routine neurological evaluation in both alcoholics and AIDS patients. Therefore, there is a need for noninvasive diagnostic procedures. Using the pyrithiamine-treated rat, an animal model of WE, we have studied, using radioligands for central (neuronal) and "peripheral-type" (glial) benzodiazepine receptors, the regional distribution of changes in the densities of these receptors in relation to the degree of reactive gliosis accompanying neuronal loss. Histological studies revealed neuronal loss in selective regions, including the thalamus, inferior colliculus, inferior olivary nucleus, and mammillary body. Autoradiographic studies demonstrated increases in densities of [3H]PK11195 binding sites that closely paralleled the topographic distribution of neuronal cell loss and reactive gliosis. In contrast, [3H]Ro15-178 showed poor spatial correlation, with the neuronal loss seen in pyrithiamine-induced thiamine deficiency. The positron emission tomography ligand [11C]PK11195 may be useful for the assessment of thiamine deficiency-induced brain damage in human alcoholics.