Focal seizures disrupt protein synthesis in seizure pathways: an autoradiographic study using [1-14C]leucine

We have used a new autoradiographic technique developed by Smith et al.22,33 for visualizing rates of incorporation of [1-14C]leucine into protein in brain. Focal seizures caused by topical convulsants resulted in a marked decrease in autoradiographic density. This was primarily confined to the seizure focus, especially marked in pyramidal cell layers, and to subcortical seizure pathways. There were no distinct changes in cortico-cortical pathways beyond the seizure focus. Pure orthodromic pathways through basal ganglia showed an 18% inhibition of leucine incorporation in caudate nucleus and substantia nigra, pars compacta (P less than 0.05). By contrast, thalamic nuclei connected both ortho- and antidromically to the focus showed a 30-63% inhibition (P less than 0.01). The topographic pattern and intensity of the thalamic changes were related to the site, size and intensity of the seizure focus. As seizures became severe there was a more generalized depression of metabolism beyond seizure pathways, especially in the ipsilateral hemisphere. The results suggest that seizures block incorporation of leucine into protein either by an increase oxidation of the precursor, and/or an inhibition of protein synthesis per se. The effect is most severe in neurons undergoing epileptic burst discharge in the focus and in thalamic neuronal beds connected reciprocally with the focus.