Effects of a restricted unilateral neocortical lesion upon cerebral glucose and oxidative metabolisms in fetal and neonatal cats

The present study was designed to measure cerebral glucose and oxidative me tabolisms and to assess relationships with previously identified morphologi cal changes in adult cats with a unilateral, restricted neocortical lesion sustained either during fetal life or neonatally. Local cerebral metabolic rates for glucose (LCMRglc) were measured using the [C-14]2-deoxy-D-glucose (2 DG) autoradiography method and oxidative capacity was determined using cytochrome oxidase histochemistry (C.O.). Only glucose metabolism in the fe tal-lesioned cats was affected substantially. There was a global decrease ( 31.0% relative to controls) of the LCMRglc for both cerebral hemispheres wh ile focal decreases were seen mainly in thalamic and neostriatal nuclei (an d reaching declines of over 50%), Cats with a neonatal lesion showed only a tendency to such declines (19.5% and 22.0% for the right and left hemisphe res, respectively). C.O, values were not affected significantly either glob ally or locally in any of the age-at-lesion groups. In previous work using fetal animals with similar lesions, morphological evidence of subcortical n europile degeneration was not observed; instead, a marked decrease in size of the ipsilateral remaining neocortex and a pronounced distortion of gyri and sulci patterns bilaterally were found. In this context, we propose that in the fetal-lesioned cats, there was a widespread lesion-induced decrease in corticofugal (and transcortical) synaptic inputs which was responsible for a decline in functional (synaptic) activities, and that this, in turn, caused a downturn in glucose utilization. In the neonatal cats minor degene ration, coupled with lack of reinnervation, would account for the tendency to 2 DG declines. These results indicate that the long-term metabolic respo nse of the fetal brain to injury is also less adaptive than that of the neo natal brain. Since standard methods are available to measure cerebral metab olism in humans, our studies in animal models may help understanding the lo ng term physiological consequences of developmental focal brain damage in p atients as well as to predict the relationships between cerebral metabolism and the underlying long-term morphological effects of such lesions. (C) 19 99 Elsevier Science B.V. All rights reserved.