Cortical perfusion assessment with 123I-isopropyl amphetamine (123I-IAMP) in normal pressure hydrocepha lus (NPH).

NPH can be reversible after cerebrospinal fluid (CSF) diversion. In the past no reliable criteria could be defined to predict the successful outcome of CSF shunting. Several authors demonstrated an increased cerebral blood flow after lumbar puncture in patients with NPH, indicating an underlying impairment of cerebral circulation autoregulation. 123I-AMP brain tomoscintigraphy was applied to 23 individuals with NPH before and after CSF drainage. Of these 23 patients, 10 underwent surgical shunting. The frontal and parietal hypoactive cortical pattern was present in NPH but not pathognomonic. Under stimulation of CSF pressure lowering, seven patients with improved outcome after shunting demonstrated an increase of cerebral perfusion in these areas, whereas a decrease of activity was found in three patients whose clinical status was unchanged after CSF diversion. This tomoscintigraphic test may be an interesting additional criterion for surgical admission.

[Cerebral glucose consumption. The effect of Ginkgo biloba extract]. / Consommation cérébrale du glucose. Effet de l'extrait de Ginkgo biloba.

Deoxyglucose is transported under the same conditions as glucose from blood to cerebral tissue. Deoxyglucose-6-phosphate, which cannot be neither metabolized nor eliminated, accumulates in cells. This accumulation is correlated with glucose consumption. In this study, two parameters, transfer rate of deoxyglucose and glucose consumption were measured by means of quantitative autoradiography in two experimental models: normobaric hypoxia and carotid clamping in rats. Normobaric hypoxia induced a decrease in both transfer rate and glucose consumption. Ligature of the carotid artery induced a diminution of glucose consumption greater than that of transfer rate. After administration of Ginkgo biloba extract, glucose consumption was partly reestablished in both experimental models, but the transfer rate of deoxyglucose was increased only in normobaric hypoxia.

[Protective effects of Ginkgo biloba extract on the early rupture of the hemato-encephalic barrier in the rat]. / Effets protecteurs de l'extrait de Ginkgo biloba sur la rupture précoce de la barrière hémoencéphalique chez le rat.

During the hours immediately following an hypertensive burst or a cerebral ischemia induced by the intracarotid administration of microspheres, damage to the blood brain barrier can be observed with molecules of low molecular weight, such as angiotensin, whereas albumin or large proteins will not yet have been able to cross over and there is virtually no edema. Gingko biloba extract causes the brain uptake index of angiotensin hypertensive animals. This effect is proportional to the dose of extract used (500-100 mg/kg). A similar effect can be observed in animals showing embolism in one hemisphere. The process can therefore doubtlessly be explained by the stabilizing effect of Ginkgo biloba on membranes.

Evidence for the role of ammonia in the intracerebral transfer and metabolism of tryptophan.

After portacaval shunt in the rat, the transport of tryptophan and other neutral amino acids across the blood-brain barrier is enhanced. To determine the role of NH3 in the intracerebral transfer of tryptophan and serotonin metabolism, solutions containing either saline or NH3 or tryptophan or NH3 + tryptophan together were infused, respectively, into the internal carotid artery of rats in order to achieve blood levels similar to those observed after liver ischemia. After tryptophan infusion, a significant increase in the hypothalamic levels of tryptophan and 5-hydroxyindoleacetic acid was observed. A similar increment was found after NH3 infusion. NH3 + tryptophan infusion induced a significant increment in hypothalamic tryptophan and 5-hydroxyindoleacetic acid levels which were 2-fold greater than after tryptophan infusion. There was no significant change in 5-hydroxytryptamine levels in any of these experiments. Glutamine levels increased significantly after NH3 infusion. When tryptophan and NH3 were infused simultaneously, a significant reduction in glutamine levels occurred. These results cannot be explained by any modification of cerebral blood flow nor of the cerebral intercellular pH. Our data suggest that NH3 enhances the transfer of tryptophan across the blood-brain barrier and thus stimulates serotonin metabolism. The mechanism by which tryptophan transfer across the blood-brain barrier is facilitated is unknown. The reduction in glutamine levels in the hypothalamus when NH3 and tryptophan are infused together may be explained either by an inhibition of synthesis or by an intercellular influx of neutral amino acids and an efflux of glutamine as suggested by James et al.

Age and learning: experimental and clinical aspects.

Memory loss and similar cognitive associated dysfunctions are commonly recognized as being the most serious symptoms of ageing and dementia. In this work, a deterioration of cognitive function which is appreciated in old rats (learning test in a maze--or, in aged humans, memory verbal test) is determined during the measurement of local cerebral blood flow and metabolism. In the animal, the disturbance by the learning test is observed by a decrease of blood flow in the hippocampus, diencephalon, and corpus striatum. In man, the cognitive dysfunctions appear although there is an increase of blood flow in the frontal cortex. These data show a new organization in the ageing brain which only appears during cerebral stimulation.

Psychometric tests in ageing.

In order to detect and analyze early cognitive disorders related to ageing, we selected a battery of psychometric techniques. This battery includes a generally accepted test (the PRM of A. Rey) and new computerized tests (reaction-time test and video objects test) designed by ourselves. We used this battery with aged adults ('normal' and 'impaired' outpatients) and young adults ('normal'). Preliminary results indicate an early decline of spatial structuralization and intellectual associative mechanisms necessary to the efficiency of memory, and also confirm the slowing down in the visual-auditory-motor coordination. The data show how new computerized techniques can be helpful tools to quantify early cognitive disorders.

Multiparametric imaging of blood flow and metabolism after middle cerebral artery occlusion in cats.

In anesthetized adult cats, acute stroke was produced by transorbital occlusion of the left middle cerebral artery. A battery of imaging techniques was used for simultaneous evaluation of regional blood flow, glucose utilization, protein synthesis, pH, and the regional tissue content of glucose, ATP, and potassium. The electrophysiological impact of stroke was monitored by EEG frequency analysis and recording of somatosensory evoked potentials. Two hours after vascular occlusion, a close correlation existed between the degree of electrophysiological changes and biochemical alterations, in particular with the extent of tissue acidosis, ATP depletion, decrease of tissue potassium content, and suppression of protein synthesis. However, there was only a poor correlation with blood flow and glucose utilization. Both of these exhibited a greatly inhomogeneous pattern with regions of reduced, normal, or increased rates. In areas remote from the infarct, the content of biochemical substrates was normal but blood flow was reduced globally by approximately 50% and glucose utilization by approximately 20%. An anatomically defined regional pattern of cerebral or cerebellar diaschisis was not observed. It is concluded that during the acute phase of stroke, imaging of blood flow and glucose utilization does not provide an accurate estimate of the actual functional or metabolic disturbance. For the clinical evaluation of the development or treatment of stroke, in consequence, alternative noninvasive techniques such as imaging of protein synthesis and/or pH may be more relevant.

Learning and cholinergic neurotransmission in old animals: the effect of Hydergine.

In the present work, a study of the number of functional receptors has been made with 3HQNB given to resting awaken animals during a learning process. Ageing leads to a decrease in the ability of learning associated with an increase in the number of large movements. The number of cholinergic receptors is also reducel if we compare 22 month old animals with 4 month old animals maintained under usual conditions. Learning conditioning leads to a stimulation of the cholinergic system with a release of acetylcholine. The mediator takes the 3HQNB out of its fixation areas which causes an apparent decrease in the number of receptors. This result is more significant in young animals than in aged ones because of the possibility of activation in the cholinergic system. The treatment by dihydroergotoxine partially re-establishes the learning abilities in animals and, at the same time, increases the number of cholinergic receptors This effect could explain the actions of this drug on the memory process in ageing persons.

Iodoamphetamine as a new tracer for local cerebral blood flow in the rat: comparison with isopropyliodoamphetamine.

Rats were injected with iodoamphetamine synthesized and labeled with 125I or with 125I- isopropyliodoamphetamine , a molecule of established value for the determination of local cerebral blood flow. The blood kinetics, tissue distribution, and brain uptake index for each tracer exhibited practically no differences. Autoradiographic quantification of the local cerebral blood flow, calculated according to the microsphere model, produced identical results for both molecules. However, compared with the values reported for other tracers, our values constituted an underestimation of white matter blood flow and a more real estimation of hippocampal flow. It is concluded from the brain uptake of the derivatives of both amphetamines during the first minutes following their injection that these tracers can be used as a chemical microembolus for the measurement of local cerebral blood flow.

Simultaneous study of haemodynamic, metabolic and behavioural sequelae in a model of cerebral ischaemia in aged rats: effects of nicergoline.

Unilateral cerebral ischaemia was induced in 18-month-old Long-Evans rats by injection of 2,000 labelled microspheres (phi 50 microns) into the carotid blood stream. This results in an ipsilateral decrease in cerebral blood flow, development of severe oedema and modifications of glucose uptake and consumption. Furthermore, this ischaemia led to a deterioration of the avoidance response in conditioned animals. All these disturbances, including the cerebral oedema, diminished with nicergoline pretreatment.

Simultaneous study of cerebral blood flow, vascular bed and deoxyglucose in aged rats. Effects of two dihydrogenated rye ergot alkaloids.

The influence of aging and the effects of treatment with dihydrogenated rye ergot alkaloid on cerebral hemodynamics and metabolism were studied in Long-Evans rats. Cerebral blood flow (CBF) was not affected by aging whereas the vascular bed and the uptake of deoxyglucose were significantly lower in aged than in young rats. 20 days after ligation of a carotid artery the blood flow on the same side of the brain, the vascular bed and the uptake of deoxyglucose were significantly lowered in aged rats as opposed to young rats. The second carotid artery was ligated 1 h before the animals were sacrificed: in the corresponding cerebral hemisphere the blood flow was found to be significantly lowered in young rats and even more so in aged rats. These results show that young rats are more likely to adapt to an acute or chronic circulatory deficiency than aged rats. Dihydroergocryptine ( DHEC , 0.1 mg/kg/day for 5 days, p.o.) reduces CBF and the vascular bed in aged rats, as opposed to dihydroergotoxine ( DHET , 5 X 0.1 mg/kg/day p.o.). The uptake of deoxyglucose was not influenced by the treatments. After ligation of the carotid arteries, treatment with DHEC and DHET induced an increase in CBF without any change in the vascular bed and, in the case of DHEC only, there was a significant increase in the uptake of deoxyglucose in the cerebral hemisphere submitted to acute circulatory deficiency. DHEC and DHET thus exerted significant effects on cerebral metabolism and hemodynamics in the aged rats after repeated oral treatment.

[Chemical and pharmacological aspects of cerebral cellular tracers]. / Aspects chimique et pharmacologique des traceurs cellulaires cérébraux.

Among the iodophenylalkylamines studied and labelled with iodine 125 or iodine 123, N-isopropyl-iodo-amphetamin (IAMP) was selected and proposed as tracer for blood flow, a "chemical embolus" having almost 100% extraction in the brain. A new way of obtaining N-isopropyl-p-iodo-amphetamin is proposed and the easily-applied exchange reaction with iodine 125 or 123 gives a product with a radiochemical purity of more than 96% and an unexchanged radioactive iodine content of less than 1%. The pharmacokinetic study of this product in the Wistar rat showed distribution in three compartments and the appearance of a steady state by the fourth minute. The target organs are the lungs, liver and brain. The latter receives 3% of the radioactivity and the autoradiographic study shows that the early distribution in the brain for IAMP closely equals the blood flow as found by a diffusible indicator. In the first hour, the redistribution is very low and at this time although IAMP is proposed for the study of regional blood flow, it does not exactly determine the flow but rather mirrors cell activity.

[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.

Demonstration of vascular redistribution after carotid clamping in rats.

In Long Evans rats, the vertebral arteries supply only the brain stem. Simultaneous application of clamps to both carotid arteries results in a considerable fall of cerebral blood flow and eventually death. If an interval of about 4 days is allowed between the clamping of the 2 carotids, redistribution of blood flow takes place. Owing to this mechanism, 50% of the rats survive with a satisfactory restoration of cerebral blood flow.

Cerebral blood-flow tomography: xenon-133 compared with isopropyl-amphetamine-iodine-123: concise communication.

Tomographic maps of local cerebral blood flow (CBF) were obtained with xenon-133 and with isopropyl-amphetamine-iodine-123 (IMP) in 11 subjects: one normal, two tumor cases, and eight cerebrovascular cases. A highly sensitive four-face, rapidly rotating, single-photon emission tomograph was used. The Xe-133 flow maps are essentially based on the average Xe-133 concentration over the initial 2 min during and after an inhalation of the inert gas lasting 1 min. These maps agreed very well with the early IMP maps obtained over the initial 10 min following an i.v. bolus injection. The subsequent IMP tomograms showed a slight decrease in contrast amounting to appr. five percentage points in the CBF ratio between diseased and contralateral areas. It is concluded that Xe-133 is more practical: low cost, available on a 7-day basis, easily repeatable, quantifiable without the need for arterial sampling, and with low radiation exposure to patient and personnel. On the other hand, IMP gives an image of slightly higher resolution. It also introduces a new class of iodinated brain-seeking compounds allowing, perhaps, imaging of other functions more important than mere blood flow.