Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

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.

Memory complaints in the elderly: a study of 367 community-dwelling individuals from 50 to 80 years old.

State of memory was evaluated by a Memory Clinic in 367 community-dwelling patients aged from 50 to 80. They performed an exhaustive subjective evaluation including: severity of memory complaint, social status, activity scale, subjective Memory score, Zung's anxiety and depression scales and Well Being Questionnaire. Objective memory performance was evaluated by a complete memory scanning leading to a Global Objective Memory Score. No relationship was found between severity of memory complaints and age, sex, educational level, marital status, living alone or in family, and memory tests performance. More severe complaints were reported in people with poor social network, negative stereotypes on aging, and poor affective status. A strong correlation was found between severity of memory complaints and scores in self-reporting depression questionnaire, even in people with low depression scores.

Biochemical and behavioural effects of hypoxic hypoxia in rats: study of the protection afforded by ergot alkaloids.

The conditioned avoidance response and the cerebral levels of dopamine and noradrenaline have been studied in control rats and in rats submitted to a hypobaric hypoxia. A protection against the effects of hypoxia was induced by both dihydroergocornine (20 microgram/kg) and dihydroergocryptine (100 microgram/kg), and the noradrenaline level did not decrease. This stabilization of cerebral noradrenaline level seems to be the main protection factor observed.

Action of cytidine diphosphocholine on functional and hemodynamic effects of cerebral ischemia in cats.

The depression of evoked cortical potentials caused by brief periods of cerebral ischemia is attenuated by prior intracarotid injection of cytidoline (2, 4 or 8 mg/kg). Studies performed in hypercapnic cats suggest that the protection afforded by cytidoline is of metabolic rather than hemodynamic origin. The participation of the central dopaminergic structures by the drug is suggested according to the previous data.

[Memorization and central catecholamines after a craniocervical injury carried out in rats: influence of imipramine administration (author's transl)]. / Mémorisation et catécholamines centrales après un traumatisme cranio-cervical expérimental chez le rat: influence d'une administration d'imipramine.

A craniocervical injury has been carried out in rats (with head free to move) so that they get through a whiplash without any coma. Two days after the whiplash, comparable with a postcommotional syndrome, the acquisition of a labyrinth behavior is disturbed and, 7 days later, the retention is still disturbed. This disturbance of retention is not observed when the acquisition is performed before the whiplash. These data agree with the clinical observations, and we hypothesize a possible causal relation between the disturbance of learning behavior and the decrease of noradrenaline cerebral level induced by the whiplash. Treatment with imipramine (1 mg/kg) after the whiplash is able to remove these behavioral and biochemical disturbances.

Cardiovascular responses to acute hypoxia in dogs pretreated with benserazide and L-DOPA.

In the control dogs, hypoxia induced different hemodynamic modifications (i.e. an increase of arterial blood pressure, heart rate, cardiac output, regional blood flow) which seem to be related to a release of epinephrine. Pretreatment with benserazide (20 mg/kg i.v.) and L-Dopa (50 mg/kg i.p.) either lessened or completely suppressed any sign of sympathetic stimulation. These results suggest that chemoreceptors are centrally inhibited as had been previously proved for baroreceptors.

[The treatment, by imipramine, of the hemodynamic, functional and biochemical consequences of an experimental cranio-cervical trauma in rats]. / Traitement, par l'imipramine, des conséquences hémodynamiques, fonctionnelles et biochimiques d'un traumatisme cranio-cervical expérimental chez le rat

The experimental reproduction of a cranio-cervical traumatism in the rat and consecutive troubles prove the organicity of the post-concussional syndrom. This syndrom seems to be due to an acceleration of the catabolism of cerebral norepinephrin, and the treatment by imipramine seems to inhibit the decrease of its rate.

[Hemodynamic study of postural regulation in the dog treated or not treated with levomepromazine]. / Etude hémodynamique de la régulation posturale chez le chien traité ou non par la lévomépromazine

Analysis of hemodynamic parameters in untreated and treated dogs (levomepromazine 5 mg/kg i.v.) during supine and erect position showed, 1) that the regulation of cerebral blood flow remained in the anaesthetized (pentobarbital 25 mg/kg i.v.) dogs ; 2) that the sympathetic reaction induced different effects in various vascular regions ; 3) that levomepromazine induced an impairement of the mechanisms involved in the regulation of the encephalic irrigation.

Reduction of hypoxia-induced disturbances by previous treatment with benserazide and L-dopa in rats.

Pretreatment by benserazide (50 mg/kg i.p.) and L-Dopa (100 mg/kg i.p.) in rats induces a reduction of the diminution of motility after hypoxia and a stabilization of cerebral blood flow during and after hypoxia. An overload of cerebral dopamine and norepinephrine seems to be the original process of this phenomenon.

[Effect of L-dopa combined with benserazide on hemodynamics and motor activity in hypoxic rats]. / Influence de la L-dopa associée au bensérazide sur l'hémodynamique et la motilité du rat en hypoxie

Pretreatment by benserazide (50 mg/kg) and L.dopa (100 mg/kg) reduces functionnal deficiency produced by hypoxic hypoxia in rats reduces hemodynamic modifications in relation to it (rheoencephalogram) without any effect on ventilation.

[Hemodynamic modifications induced by hypoxia in the dog]. / Modifications hémodynamiques provoquées par l'hypoxie chez le chien

In non hypercapnic hypoxia (inhalation of a 4,5% O2 mixture during 10 minutes) blood pressure, heart rate, cardiac output, femoral and carotid blood flow inhance so that, in less extent, vertebral blood flow. Such a reaction is consequent with an hypoxic stimulation of adrenal glands.