Temporal profile of interneuron and pyramidal cell protein synthesis in rat hippocampus following cerebral ischemia

Abstract

Cellular protein synthesis was investigated in the rat hippocampus 2–100 h following 20 min of cerebral ischemia induced by four-vessel occlusion. [³H]-Phenylalanine was retrogradely infused through the external carotid artery for 30 min. This method limited the distribution of the tracer to one hemisphere and required 1/50th of the tracer amount used for intravenous tracer infusion. Cellular [³H]phenylalanine incorporation was examined in hematoxyline and eosin-stained sections coated with nuclear emulsion. A score for relative protein synthesis was estimated from counts of silver grains across neuron somata with undamaged morphology. Shortly after ischemia a generalized complete arrest of protein synthesis was observed. In CA1 pyramidal cells, this was followed by a transient incomplete regeneration (9–20 h) and later (46–100 h) persistent cessation of protein synthesis. By contrast protein synthesis in interneurons, CA3c pyramidal cells and granule cells recovered to preischemic levels 9–100 h after ischemia, as did the CA3ab pyramidal cells 46–100 h postischemia. Moreover, eosinophilic cell changes were seen in hilar and CA3c neurons at all postischemic stages and in CA1 pyramidal cells 46–72 h after ischemia. [³H]Phenylalanine incorporation was absent in neurons demonstrating eosinophilic cell changes. From the rapid recovery of protein synthesis in hippocampal interneurons, we conclude that changes in interneuronal protein synthesis per se are not involved in the pathophysiology of the delayed ischemic CA1 pyramidal cell death.