Neuronal response of the hippocampal formation to injury: Blood flow, glucose metabolism, and protein synthesis

Abstract

The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([ 123I]isopropyl-iodoamphetamine [IMP]), glucose utilization ([ 14C]2-deoxyglucose), and protein synthesis ([ 14C]leucine), using single- and double-label autoradiography. Our study showed (i) decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; (ii) increased uptake of [ 123I]IMP around the lesion from 1 to 3 days postlesion; and (iii) starting 3 days after the lesion, marked decrease in [ 14C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury.