Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment.

This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug.

[Learning, hemodynamic and metabolic attendant effects in aged animals after an acute ischemic accident]. / Apprentissage et concomitances hémodynamiques et métaboliques chez l'animal âgé après un accident ischémique aigu.

The effects of ageing in normal and pathological rats were studied. Learning (spatio-temporal test) was measured simultaneously with the local cerebral blood flow, determined by a diffusible indicator (iodoantipyrine) and with the uptake and consumption of glucose, determined by the deoxyglucose. Normal ageing disturbs the learning with a decrease in acquisition speed and an increase in the number of errors. Furthermore, normal ageing induces a decrease in glucose uptake and in glucose consumption in the brain structures such as hippocampus or corpus striatum, with only a slight decrease in local cerebral blood flow. Dihydroergotoxine partially reestablishes the performances of the rats and increases the glucose consumption in the areas involved in learning. Pathological ageing, produced by the administration of microspheres and corresponding to the multi-infarct dementia, is correlated to a large decrease in glucose consumption and local blood flow. Dihydroergotoxine treatment partially suppresses the micro-infarct effects before the reestablishment of rat performance in behavioral tests.