[Chemical and pharmacological aspects of cerebral cellular tracers].
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Amphetamines↗
Biomedical subjects
J R Rapin
Publications and source records attributed to J R Rapin.
[Cerebral ischemia after ligature of both carotid arteries in rats: effect of ginkgo biloba extracts (author's transl)].
Simultaneous ligature of both carotid arteries in Long Evans rats results in death for all animals. 50% of the animals survive if the ligatures are separated by a four-day interval. Studies of variations in cerebral blood flow according to the time interval between the two ligatures show that alternative vascularization develops and that the balance between both hemibrains is restored. After giving L-dopa3H to animals with ligature of both carotids, increased synthesis of cerebral dopamine 3H and norepinephrine 3H can be demonstrated. When animals are given extracts of Ginkgo biloba leaves prior to carotid ligatures, survival rate is improved and dopamine synthesis increased, without marked changes in cerebral blood flow. This is related to increased brain cell activity in spite of hypoxia due to carotid ligature.
Animals↗
Early changes in blood-brain barrier permeability after porto-caval shunt and liver ischaemia.
The brain oedema, distribution space (DS) and brain uptake index (BUI), of L-glucose, inulin, B12 vitamin and of three polypeptidic hormones of increasing molecular weight (angiotensin-I, gastrin and insulin) were measured in the rat after sham operation, porto-caval shunt (PCS) or liver ischaemia. At an early stage following PCS or liver ischaemia brain oedema was not constant, and was only demonstrable after liver ischaemia in a large number of animals. Substances without an active transport and with a low diffusion coefficient such as L-glucose and inulin had a very low BUI, unchanged even if the 3H2O brain content or the DS were modified. B12 vitamin, DS and BUI were very high and did not change after liver ischaemia or PCS. Insulin DS and BUI were low in the three groups of animals, whereas it decreased after PCS for gastrin. A significant increase of BUI and DS (without any cerebral oedema) was demonstrated for angiotensin-I, a polypeptidic hormone of molecular weight 1300. This polypeptidic marker is in the same range of MW as the preliminary recently recognized medium-sized molecules which may be involved in the pathogenesis of encephalopathy during experimental acute liver failure. However, not only the MW, but the nature of such polypeptides may be of importance in the genesis of this limited impairment of BBB permeability.
Acute Disease↗
[Cerebral blood flow metabolism and behavior following cerebral infarction in the awake rat (author's transl)].
In the awake rats, a cerebral ischemia was performed by means of 2,000 microspheres administered into the internal carotid via a chronic catheter. After a coma lasting for a few minutes and a 24-48 h palsy, the Long Evans rats gradually recover a normal behavior. The acquisition of an avoidance response is deeply disturbed by microembolization but the capacities of memorization reappeared with the regression of oedema. 7 days after embolization, the cerebral blood flow in ischemized hemisphere was still significantly decreased, and in spite the glucose consumption was identical in ischemized and non ischemized side. This latter parameter is a better index of the cell activity. This model in the awake rat was proposed for the study of molecules used in cerebral ischemia without interference of anesthetics drugs.
Animals↗
[Drug protection of cerebral metabolism and behavioral activity after an acute ischemic stroke].
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Acute Disease↗
Effects of naftidrofuryl on cerebral hemodynamics, metabolism and function after a retracted ischaemia.
Unilateral microemboli were formed in the brains of Long Evans rats by means of an intracarotid injection of microspheres (50 mu). This embolization resulted in a decrease in blood flow, severe cerebral oedema and a modification of glucose uptake. Furthermore, these microemboli affected a conditioned avoidance response. Naftidrofuryl enabled a better recovery of the processes involved in the expression of acquisition. This has been related to a decrease in the development of oedema on one side and to a better glucose uptake on the other. These data demonstrated that naftidrofuryl influences the sequelae of rapidly regressive ischaemia.
Animals↗
Deoxyglucose uptake in pathological conditions.
In case of quick physiological variations or in pathological conditions, it is impossible to measure the deoxyglucose consumption by means of the deoxyglucose technique and we propose a method for the study of the deoxyglucose uptake by the cerebral tissue. It is simultaneously measured with the blood flow, 3 min following the intravenous administration of deoxyglucose (2-deoxyglucose-14C). Hypercapnia induces an increase in the flow but does not modify the deoxyglucose uptake and moderate hypoxia results in a decrease in the deoxyglucose uptake without modifying the flow. In pathological conditions such as ischemia or stricture, the blood flow and deoxyglucose uptake variations are not parallel. These results show that the 2-deoxyglucose uptake does not follow the blood flow and that it depends on the cell activity. It is therefore possible to use this method when the consumption studies cannot be implemented.
Animals↗
Specific behavior-bound brain cartography of the glucose uptake rate.
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Animals↗
Short-term memory and cerebral ischemia: pharmacological application.
Transient ischemia results in changes in the cerebral blood flow at the level of microinfarcts, enzymatic and metabolic changes and the development of a cerebral edema; all these disorders regress in the week following ischemia. Besides, the observed functional disorders disappear as the cerebral edema regresses. The brain functional activity is protected by the use of treatments which reduce the development of the cerebral edema and/or a quicker regression of the edema.
Animals↗
[Cerebral blood flow, metabolism and learning after a cerebral infarction in the rat (author's transl)].
Experimental microembolization of the rat brain has been used as a model for the production of cerebral microinfarction which resulted in a decrease in blood flow and secondary brain edema with changes in the oxidative metabolic pathways. The use of radioactive microspheres as embolizing agents allowed to determine the number of microinfarctions and their localization. In every microinfarct, oedema developed and it could be quantified by measuring the water percentage as soon as the fourth hour following the microembolization. The activity of oxygen-dependent enzymes was severely reduced in the ischemic area around which hyperemia was present. A quick decrease in the ATP and glucose levels and an increase in the lactate levels were observed, showing that the energetic metabolism was deviated towards the anaerobic pathway. On the fifth day following the microembolization, the oedema disappeared. The cellular metabolic activity and the cerebral blood flow almost returned to normal values within the same time. The simultaneously study of an avoidance response in a conditioned learning test showed a correlation between the reappearance of this response and the regression of the oedema.
Animals↗
Correlation between brain blood flow and catecholamine levels in rat brain areas under hypobaric hypoxia.
Hypobaric hypoxia induces an important increase in the cerebral blood flow in all areas and more particularly in the bulb and hypothalamus; the increase in the cerebral blood flow allows for an oxygen intake sufficient to maintain the norepinephrine level in these structures.
Animals↗
Age-associated changes in deoxyglucose uptake in whole brain.
Cerebral blood flow, studied by means of a diffusible indicator, remains unchanged in the aging process (developmental changes). On the contrary, brain activity, evaluated by deoxyglucose uptake, is significantly reduced. Papaverine, which increases cerebral blood flow, and vincamine, slightly but significantly, act on this parameter in the older animals.
Aging↗
[Effects of oxilofrine on the activity of the sympathetic nervous system (author's transl)].
The effects of 1-(4-hydroxyphenyl)-2-methylamin-propanol- (1) (oxilofrine, 4-HMP) on the catecholamine metabolism were investigated in vitro in isolated rat hearts and spleen sections. Investigations were conducted in vivo to determine the influence exerted by the sympathomimetic agent on the noradrenaline biosynthesis in the heart and on the oxygen-dependent enzymes tyrosine hy droxylase and dopamine-beta-hydroxylase. Oxilofrine is an excellent inhibitor of the noradrenaline storage in the heart (DI = 1.5 X 10(-6) mol/l). At the same time, the sympathomimetic agent releases noradrenaline from the storage compartments. In this process, preferably newly synthetised noradrenaline is released both from the heart and from the spleen. This double mechanism of action is associated with an acceleration of the noradrenaline biosynthesis and an increase in enzymal activity of tyrosine hydroxylase and dopamine-beta-hydroxylase. The transmitter concentrations in the region of the postsynaptic receptors are enhanced by oxilofrine.
Animals↗
[Presynaptic adrenergic mechanisms of action of oxilofrin].
The presynaptic adrenergic mechanisms of action of 1-(4-hydroxyphenyl)-2-methylamino-propanol-(1) (4-HMP, oxilofrine) were investigated in the rat. The sympathicomimetic agent is stored in the heart by a mechanism with saturation characteristics, resembling noradrenaline in this respect. Inhibitors of the neuronal and extraneural binding of noradrenaline at the same time suppress the tissular uptake of 4-HMP. Investigations in vivo in the tissular distribution and on the subcellular distribution in the iris, vas deferens and spleen confirm the affinity of 4-HMP for the storage vesicles containing noradrenaline. Stimulation of the spinal nerves results in a release of the sympathicomimetic agent. This underlines the significance of the presynaptic mechanisms of action for the pharmacological properties of 4-HMP.
Animals↗
[Effects of oxilofrine on the release and storage of noradrenaline in cardiac sections of the rat (author's transl)].
Experiments in vitro have shown 1-(4-hydroxyphenyl)-2-methylamino-propanol-(1) (oxilofrine, 4-HMP) to release noradrenaline from cardiac ventricular sections. This effect sets in at a concentration of 10(-5) mol/l and reaches the 30% level at 5X10(-5) mol/l. The inhibition of noradrenaline storage is still more pronounced. At 5 X 10(-5) mol/l the inhibition is 60%. The significance of both mechanisms of action of the sympathomimetic agent is discussed in comparison with compounds of related structure.
Animals↗
Blockade of the different enzymatic steps in the synthesis of brain amines and memory (CAR) in hypobaric hypoxic rats treated and untreated with L. dopa.
L. Dopa associated with an extracerebral inhibitor of dopadecarboxylase is able to protect the rat against the deleterious effects of hypobaric hypoxia on a conditioned avoidance response. L. Dopa loses its protective effect against hypoxia if tyrosine hydroxylase, dopadecarboxylase, or dopamine beta hydroxylase is previously blocked. L. Dopa's protective effect must therefore be due to an indirect action on the endogenous catecholamine metabolism.
Acoustic Stimulation↗
Effects of Ginkgo Biloba on changes induced by quantitative cerebral microembolization in rats.
Unilateral embolization of the brain was performed in rats by the intracarotid injection of 4000 radioactive microspheres (50 micron). The local blood flow was determined using the iodoantipyrine technique in the hippocampus, hypothalamus, striatum and remainder of the brain. Embolization resulted in a decrease in the blood flow and a modification of the distribution of microflow. Besides, the embolization produced changes in energy metabolism, specially a fall in ATP and glucose levels and an increase in lactate level. Subsequently severe vasogenic cerebral edema developed. There was a correlation between the number of microspheres injected and the extent of edema. Pretreatment with an extract of Ginkgo Biloba leaves partially suppressed the effects of the embolization. An increase in the blood flow associated with normalization of cellular energy metabolism explained the decrease in brain edema.
Adenosine Triphosphate↗
The effect of various stimulated altitudes on the turnover of norepinephrine and dopamine in the central nervous system of rats.
The elimination rate constant, half-life and turnover time of dopamine (DA) and norepinephrine (NE) were determined, after inhibiting their biosynthesis by alpha-methyl-para-tyrosine (alpha MT), in the hypothalamus, striatum and the remainder of the brain of rats exposed to different degrees of hypobaric hypoxia, corresponding to altitudes of 1,800, 3,800, 5,200 and 7,000 meters. The effects varied as a function of the degree of hypoxia and the brain region studied. The turnover time of NE in the hypothalamus remained unchanged, regardless of the altitude, while in the rest of the brain the rate constant of neurotransmitter elimination decreased inversely as a linear function of the degree of hypoxia. On the contrary, the changes of the DA turnover time in the striatum and the rest of the brain, were biphasic, being accelerated by moderate altitudes (1,800 m) and retarded by the two highest simulated altitudes studied as a function of hypoxia. The differential effects of hypoxia on NE and DA turnovers are attributed to different sensitivities of the respective enzyme systems.
Altitude↗