Cerebral glucose utilization: local changes after microinoculation of scrapie agent in hamster

The effects of scrapie agent on local cerebral energy metabolism were studied by the [14C]2-deoxyglucose (2-DG) autoradiographic method of Sokoloff et al. after stereomicroinoculation (0.5 microliter, 10(-2) of scrapie suspension) in hamster left striatum. From a group of 20 hamsters inoculated, 2 animals were killed every 10 days from the 30th day after inoculation to the terminal stage of the disease. Experiments were carried out according to the qualitative 2-DG procedure and cerebral autoradiographs of inoculated animals were compared to those of 3 controls. The results show changes of local cerebral glucose utilization in some discrete brain regions, ipsilateral to the side of inoculation, and their sequential spreading to other cerebral structures with a definite order: left anterior thalamus, left posterior thalamus, then medial geniculate body (ipsilateral, then controlateral), and finally some brainstem nuclei (inferior colliculus, superior olivary nucleus); the inoculated striatum is affected very late, after clinical signs. Metabolic changes which first occur ipsilaterally to the side of inoculation precede the clinical symptoms, while their contralateral spreading is concomitant with the clinical signs. The data demonstrate a rostral--caudal sequence of the cerebral metabolic changes, ipsilateral to the side of inoculation, which may reflect in part the slow spread of agent in the central nervous system from the inoculation site.