A morphometric and immunohistochemical study of the vestibular nuclear complex in bovine spongiform encephalopathy.

A morphometric and immunohistochemical study of the vestibular nuclear complex was performed on five bovine spongiform encephalopathy (BSE) and five control cow brains. Neurons of the lateral and superior vestibular nuclei were counted at 500-microns intervals in 10-microns-thick sections, using an image analysis system comprising a projection microscope and digitising pad linked to a computer. A bimodal distribution of neuron diameters was recognised in the brains of normal cattle. One population of neurons had a mean diameter of 30 microns and the other had a mean diameter of 60 microns. The vestibular nuclei from BSE cattle had an approximately 50% reduction in total numbers of neurons when compared with controls (P < 0.01). Cattle which were clinically diseased longer had the fewest number of neurons preserved. Diminished numbers of neurons were detected throughout the area studied and affected neurons of all diameters. Immunohistochemical staining for synaptophysin, a protein present in synapses throughout the CNS, showed no significant reduction in axon terminals synapsing with vestibular neurons, including vacuolated neurons of BSE brains, when controls and BSE brains were compared. This suggests that de-afferentation of neurons is not the cause of neuronal loss. Prion protein was detected in the neuropil of the vestibular nuclear complex of BSE brains but not control brains. These studies show that previously unsuspected neuronal loss is a significant feature of BSE.