ABSTRACT
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.
Subject(s)
Brain/radiation effects , Cognition Disorders/etiology , Cognition/radiation effects , Aging , Animals , Avoidance Learning/radiation effects , Male , Radiation, Ionizing , Rats , Rats, WistarABSTRACT
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.
Subject(s)
Brain Ischemia/complications , Brain Ischemia/metabolism , Hippocampus/metabolism , Memory Disorders/etiology , Nafronyl/therapeutic use , Nerve Tissue Proteins/biosynthesis , Animals , Brain Ischemia/drug therapy , Cerebrovascular Circulation/drug effects , Memory/drug effects , Memory Disorders/drug therapy , Memory Disorders/psychology , Rats , Rats, Inbred StrainsABSTRACT
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.
Subject(s)
Aging/physiology , Memory Disorders/physiopathology , Memory/physiology , Aged , Aged, 80 and over , Community Mental Health Services , Depression/pathology , Female , Humans , Male , Memory Disorders/diagnosis , Mental Recall/physiology , Middle Aged , Neuropsychological Tests , Retention, Psychology/physiology , Surveys and QuestionnairesSubject(s)
Kidney/diagnostic imaging , Succimer , Sulfhydryl Compounds , Animals , Autoradiography , Carbon Radioisotopes , Kidney/metabolism , Male , Radionuclide Imaging , Rats , Rats, Inbred Strains , Receptors, Drug/analysis , Succimer/metabolism , Technetium , Technetium Tc 99m Dimercaptosuccinic AcidSubject(s)
Neck Injuries , Whiplash Injuries/complications , Animals , Behavior, Animal , Cerebrovascular Circulation , Dopamine/metabolism , Female , Norepinephrine , Rats , SyndromeABSTRACT
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.
Subject(s)
Avoidance Learning/drug effects , Catecholamines/metabolism , Ergoloid Mesylates/pharmacology , Hypoxia, Brain/metabolism , Animals , Brain/metabolism , Dihydroergotoxine/pharmacology , Dopamine/metabolism , Dose-Response Relationship, Drug , Female , Hypoxia, Brain/prevention & control , Norepinephrine/metabolism , RatsABSTRACT
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.
Subject(s)
Blood Pressure/drug effects , Choline/analogs & derivatives , Cytidine Diphosphate Choline/therapeutic use , Heart Rate/drug effects , Ischemic Attack, Transient/drug therapy , Animals , Cats , Cerebral Cortex/drug effects , Drug Evaluation, Preclinical , Evoked Potentials/drug effects , Female , Ischemic Attack, Transient/physiopathologyABSTRACT
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.
Subject(s)
Behavior, Animal/drug effects , Brain Chemistry/drug effects , Imipramine/pharmacology , Memory/drug effects , Norepinephrine/metabolism , Whiplash Injuries/metabolism , Animals , Disease Models, Animal , Norepinephrine/analysis , RatsSubject(s)
Benserazide/therapeutic use , Cerebrovascular Circulation/drug effects , Hydrazines/therapeutic use , Hypotension, Orthostatic/drug therapy , Levodopa/therapeutic use , Posture , Benserazide/administration & dosage , Drug Therapy, Combination , Female , Humans , Levodopa/administration & dosage , MaleSubject(s)
Avoidance Learning/physiology , Brain/metabolism , Catecholamines/metabolism , Hypoxia/metabolism , Animals , RatsABSTRACT
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.
Subject(s)
Benserazide/pharmacology , Hemodynamics/drug effects , Hydrazines/pharmacology , Hypoxia/physiopathology , Levodopa/pharmacology , Animals , Blood Gas Analysis , Blood Pressure/drug effects , Cardiac Output/drug effects , Dogs , Heart Rate/drug effects , Regional Blood Flow/drug effects , Respiration/drug effects , Vascular Resistance/drug effectsABSTRACT
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.
Subject(s)
Cerebrovascular Circulation/drug effects , Methotrimeprazine/pharmacology , Posture , Animals , Blood Pressure , Carotid Arteries , Dogs , Female , Heart Rate , Hemodynamics , Hypotension, Orthostatic/physiopathology , Male , Sympathetic Nervous System/physiology , Vascular Resistance , Vertebral ArteryABSTRACT
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.
Subject(s)
Brain Injuries/drug therapy , Imipramine/therapeutic use , Spinal Injuries/drug therapy , Animals , Avoidance Learning/physiology , Behavior, Animal/physiology , Blood Pressure , Brain/metabolism , Brain Injuries/physiopathology , Dopamine/metabolism , Electromyography , Female , Heart Rate , Norepinephrine/metabolism , Posture , Rats , Spinal Injuries/physiopathologyABSTRACT
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.
Subject(s)
Benserazide/therapeutic use , Hydrazines/therapeutic use , Hypoxia/drug therapy , Levodopa/therapeutic use , Animals , Benserazide/pharmacology , Brain Chemistry , Carbon Dioxide/blood , Cerebrovascular Circulation/drug effects , Dopamine/analysis , Female , Hypoxia/physiopathology , Levodopa/pharmacology , Motor Activity/drug effects , Norepinephrine/analysis , Oxygen/blood , RatsABSTRACT
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.
Subject(s)
Benserazide/pharmacology , Hemodynamics/drug effects , Hydrazines/pharmacology , Hypoxia/physiopathology , Levodopa/pharmacology , Motor Activity/drug effects , Animals , Blood Pressure/drug effects , Carbon Dioxide/blood , Cerebrovascular Circulation/drug effects , Female , Heart Rate/drug effects , Oxygen/blood , RatsABSTRACT
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.