Biomedical subjects

J Seylaz

Publications and source records attributed to J Seylaz.

At least 37 records · Page 2Linked to original sources

PubMed1997

Reduced cortical vasodilatory response to stimulation of the nucleus basalis of Meynert in the aged rat and evidence for a control of the cerebral circulation.

In earlier studies we showed that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large increases in cerebral blood flow, mainly through cholinergic mechanisms. We then investigated the effect of aging on this influence by measuring cortical blood flow (CoBF) and tissue gas partial pressures (PtO2, PtCO2) in the conscious young adult and aged rat. NBM stimulation increased frontal (+101%) and parietal (+29%) CoBF in young rats. The effects were halved in aged rats. Moreover, PtO2 was significantly increased in young but not in aged rats. By contrast, the corticovascular reactivity to hypercapnia did not differ between young and aged rats, nor did the potentiating vasodilator effect of physostigmine. In combined autoradiographic measurements of cerebral blood flow and cerebral glucose utilization, we recently found that the cortical circulatory response to NBM stimulation was not accompanied by significant metabolic change. Thus, the blood flow changes observed in the cortex cannot be ascribed to increased metabolic activity. The distribution of this uncoupling coincides with that of cholinergic NBM projections directly impinging on cortical microvessels. These data support the cortical microcirculation and suggest the possible involvement of NBM dysfunction in the pathology of cortical microcirculation.

Aging↗

PubMed1997

Cerebrovascular consequences of altering serotonergic transmission in conscious rat.

Many therapeutic strategies aim at altering serotonin brain levels. However, serotonin (5-HT) is known to influence the cerebral circulation. The purpose of this study was to determine the effects of acutely decreasing intracerebral serotonin release upon cerebral blood flow and cerebrovascular reactivity to hypercapnia in conscious rats. To this end, (1) we analyzed the time-course of cortical blood flow changes measured with laser-Doppler flowmetry following injection of 0.1 mg kg(-1) 8-OHDPAT (5-HT1A agonist), and (2) we evaluated the cerebrovascular reactivity to hypercapnia using a quantitative multiregional diffusible tracer technique 5 and 60 min following 8-OHDPAT administration. 8-OHDPAT induced a rapid and transient increase in cortical blood flow (+34%) that was prevented totally by WAY100135 (5-HT1A antagonist) pre-treatment. Five min following 8-OHDPAT administration, the cerebrovascular responsiveness to hypercapnia was increased significantly in striatum (+27%) and fronto-parietal cortex (+61%). This result is consistent with a vasoconstrictor role of the serotonergic system that becomes manifest during hyperemic conditions.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

The effects of a butanediol treatment on acute focal cerebral ischemia assessed by quantitative diffusion and T2 MR imaging.

Increased water T2 values indicates the presence of vasogenic edema. Decreased apparent diffusion coefficient (ADC) maps reveal ischemic areas displaying cytotoxic edema. ADC and T2 abnormalities spread through the middle cerebral artery (MCA) territory up to 24 h after middle cerebral artery occlusion (MCAO). Also, it was found that ADC and T2 contours closely match at 3.5 and 24 h. Since butanediol reduces vasogenic edema and improves energy status in various models of ischemia, we used these two techniques to investigate putative improvements in cytotoxic and vasogenic edema after permanent MCAO performed on rats. Rats were given no treatment (n = 8), or a treatment with 25 mmol/kg intraperitoneal (i.p.) butanediol (n = 5), 30 min before and 2.5 h after MCAO. Quantitative ADC and T2 maps of brain water were obtained, from which the volumes presenting abnormalities were calculated at various time points up to 24 h. Effects of butanediol on the ADC and T2 values in these areas were determined. Butanediol reduced neither the ADC volume nor the initial ADC decline. However, it reduced T2 volumes by 32% at 3.5 h and 15% at 24 h (p < 0.05), and reduced T2 increase in the striatum at 3.5 h post-MCAO. Therefore, our results show for the first time that a pharmacological agent such as butanediol can delay the development of vasogenic edema but does not limit the development of vasogenic edema but does not limit the development of cytotoxic edema. ADC imaging detects areas of severe metabolic disturbance but not moderately ischemic peripheral areas where butanediol is presumed to be more efficacious.

Animals↗

PubMed1997

Effect of sympathectomy on the phenotype of smooth muscle cells of middle cerebral and ear arteries of hyperlipidaemic rabbits.

This study was carried out to determine whether sympathectomy influences the phenotypic modulation of smooth muscle cells in the peripheral and cerebral arteries of heritable hyperlipidaemic rabbits. Unilateral superior cervical ganglionectomy (common origin of innervation to the middle cerebral artery and the central ear artery) was performed on four Watanabe heritable hyperlipidaemic rabbits. Cross-sections of the ipsi- (sympathectomized) and the contralateral (intact) cerebral and ear arteries were prepared 2 months later and labelled with monoclonal antibodies against vimentin and desmin, two markers of the differentiation of smooth muscle cells, and alpha-smooth muscle actin, a marker of these cells. Sections from control and sympathectomized arteries were analysed with a confocal laser scanning microscope. Compared with contralateral intact ear arteries, the sympathectomized ear artery developed a thickened intima with dedifferentiated smooth muscle cells, expressing alpha-smooth muscle actin but no desmin, whereas the middle cerebral artery remained unchanged. These results suggest that sympathectomy may favour the progression of atherosclerosis in peripheral but not in cerebral arteries of Watanabe heritable hyperlipidaemic rabbits.

Actins↗

PubMed1997

Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate.

In a previous study, we reported that the sustained increase in CBF concomitant with seizures induced by kainate is mainly due to the potent vasodilator nitric oxide (NO). However, the production site of NO acting at cerebral vessels was undetermined. In the present study, we investigated whether NO responsible for the cerebral vasodilation is of either neuronal or endothelial origin. We used a putative selective inhibitor of neuronal NO synthase, 7-nitro indazole (7-NI). CBF was measured continuously in parietal cortex by means of laser Doppler flowmetry in awake rats. Systemic variables and electroencephalograms were monitored. Kainate (10 mg/kg i.p.) was given to rats previously treated with saline (n = 8) or 7-NI (25 mg/kg i.p., n = 8) or L-arginine (300 mg/kg i.p., n = 8) followed 30 min later by 7-NI (25 mg/kg i.p.). Under basal conditions, 7-NI decreased CBF by 27% without modifying the mean arterial blood pressure. Under kainate, 7-NI prevented significant increases in CBF throughout the seizures despite sustained paroxysmal electrical activity. L-arginine, the substrate in the production of NO, prevented any decrease in CBF under 7-NI in basal conditions and partially, but nonsignificantly, reversed the cerebrovascular influence of 7-NI during seizures. In a separate group of rats (n = 6), inhibition of cortical NO synthase activity by 7-NI was assayed at 73%. The present results show that neurons are the source of NO responsible for the cerebrovascular response to seizure activity after kainate systemic injection.

Animals↗

PubMed1997

Autoradiographic evidence for flow-metabolism uncoupling during stimulation of the nucleus basalis of Meynert in the conscious rat.

We earlier reported that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large cerebral blood flow increases, particularly in frontal cortical areas but also in some subcortical regions. The present study was designed to address the issue of blood flow control exerted by NBM projections. To this aim, we have determined whether these flow increases were associated with proportionate changes in metabolic activity as evaluated by cerebral glucose utilization (CGU) strictly under the same experimental conditions in the conscious rat. An electrode was chronically implanted in a reactive site of the NBM as determined by laser-Doppler flowmetry (LDF) of the cortical circulation. One to two weeks later, while the cortical blood flow was monitored by LDF, we measured CGU using the [14C]2-deoxyglucose autoradiographic technique during unilateral electrical stimulation of the NBM, and analyzed the local flow-metabolism relationship. The large increases in cortical blood flow induced by NBM stimulation, exceeding 300% in various frontal areas, were associated with at most 24% increases in CGU (as compared with the control group) in one frontal area. By contrast, strong increases in CGU exceeding 150% were observed in subcortical regions ipsilateral to the stimulation, especially in extrapyramidal structures, associated with proportionate CBF changes. Thus, none of the blood flow changes observed in the cortex can be ascribed to an increased metabolic activity, whereas CBF and CGU were coupled in many subcortical areas. This result indicates that different mechanisms, which do not necessarily involve any metabolic factor, contribute to the regulation of the cerebral circulation at the cortical and subcortical level. Because the distribution of the uncoupling is coincident with that of cholinergic NBM projections directly reaching cortical microvessels, these data strongly support the hypothesis that NBM neurons are capable of exerting a neurogenic control of the cortical microcirculation.

Animals↗

PubMed1997

Local uncoupling of the cerebrovascular and metabolic responses to somatosensory stimulation after neuronal nitric oxide synthase inhibition.

It has recently been shown, using either genetically engineered mutant mice (nitric oxide synthase [NOS] knockout) or specific pharmacological tools, that type I NOS (neuronal isoform of NOS, [nNOS]) participates in coupling cerebral blood flow to functional activation. However, it has not been clearly established whether the associated metabolic response was preserved under nNOS inhibition and whether this action was exerted homogeneously within the brain. To address these issues, we analyzed the combined circulatory and metabolic consequences of inhibiting the nNOS both at rest and during functional activation in the rat anesthetized with alpha-chloralose. Cerebral blood flow and cerebral glucose use (CGU) were measured autoradiographically using [14C]iodoantipyrine and [14C]2-deoxyglucose during trigeminal activation induced by unilateral whiskers stimulation in vehicle- and 7-nitroindazole-treated rats. Our data show that inhibition of nNOS globally decreased CBF without altering CGU, indicating that NO-releasing neurons play a significant role in maintaining a resting cerebrovascular tone in the whole brain. During whisker stimulation, nNOS inhibition totally abolished the cerebrovascular response only in the second order relay stations (thalamus and somatosensory cortex) of the trigeminal relay without altering the metabolic response. These findings provide evidence that the involvement of neurally-derived NO in coupling flow to somatosensory activation is region-dependent, and that under nNOS inhibition, CBF and CGU may vary independently during neuronal activation.

Animals↗

PubMed1997

NE inhibits cerebrovascular mast cell exocytosis induced by cholinergic and peptidergic agonists.

Autonomic and sensory nerves frequently contact mast cells contained in rabbit leptomeningeal arteries. We have previously shown that parasympathetic and peptidergic neurotransmitters can stimulate mast cell granule exocytosis and serotonin (5-HT) release. In the present study, we examined ex vivo the possible action of the main sympathetic neurotransmitter, norepinephrine (NE), on this exocytotic process. NE, which had no effect on mast cell 5-HT content per se, totally inhibited carbachol-induced 5-HT release and partially reduced neuropeptide-induced 5-HT release. Pretreatment with the alpha 1-adrenergic blocker did not affect the inhibitory effect of NE. Pretreatment with specific beta 1- or beta 2-adrenergic blockers antagonized this action, but the beta 2-blocker exerts a more specific dose-dependent antagonism. Together with our previous data, these results indicate that the equilibrium between autonomic and sensory nerves may determine the release of 5-HT from mast cells (parasympathetic and sensory nerves can trigger exocytosis while the sympathetics can inhibit it). Such a mechanism could be implicated in pathophysiological events in which autonomic dysfunction is likely to be involved, such as vascular headache or other phenomena involving inflammation.

Adrenergic Antagonists↗

PubMed1997

Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) of water should be sensitive to the cytotoxic edema triggered by energy failure during ischemia. Elevated values of T2. the nuclear MR transverse relaxation time of water, seen on T2 nuclear MR images detect vasogenic edema and infarcted areas. The temporal and spatial changes in ADC and T2 abnormalities after occlusion of the middle cerebral artery (MCAO) were therefore estimated by these two quantitative techniques. METHODS: Permanent MCAO was performed on rats. Quantitative ADC and T2 maps of brain water were obtained, from which the ischemic volumes were calculated at various times up to 48 hours after MCAO. RESULTS: The areas of decreased ADC represented 36 +/- 7% of the final infarct volume (24 hours) at 0.5 hours and 64 +/- 4% at 5 hours after MCAO, suggesting that there is recruitment of peripheral areas with disturbed energy metabolism and cytotoxic edema. The ADC and T2 contours closely matched at 3.5, 24, and 48 hours after MCAO. CONCLUSIONS: T2 imaging can assess ischemic insults as well as ADC imaging, but only 3.5 hours after the onset of ischemia. Assessment of edematous swelling (approximately 24.5% of total infarcted volume) demonstrates that ADC and therefore T2 imaging detect all the tissue that will become infarcted approximately 7 hours after occlusion. The spread of ADC and T2 abnormalities would therefore stop at approximately 7 hours, and any further increase in volume observed on the images would be mainly due to edematous swelling.

Animals↗

PubMed1997

Cerebral postischemic hyperperfusion assessed by Xenon-133 SPECT.

UNLABELLED: In this study, the functional and clinical evolution of the cerebral postischemic hyperperfusion (CPH) were evaluated. METHODS: Forty-four noncomatose patients suffering from unilateral cerebral ischemia located in the internal carotid territories were studied. Twenty-five consecutive patients having CPH with 133Xe-SPECT cerebral blood flow (CBF) measurement and 19 patients without cerebral hyperperfusion matched for age. CBF, vasoreactivity to acetazolamide and the evolution of the clinical state, scored by the National Institutes of Health scale for stroke, were compared. RESULTS: CPH coincided with CT-scan abnormalities in 57% of cases. The mean cerebral vasoreactivity to acetazolamide was comparable in the two groups, but there was local vasoplegia in the hyperperfused areas in 20% of CPH patients, including two cases (8%) with a steal syndrome. Comparison of the initial and late clinical scores showed no significant difference between patients with and without CPH. For patients without CPH, the interhemispheric CBF asymmetry was correlated with the initial and the late scores (p < 0.0001, r = 0.81). For the CPH group, the interhemispheric asymmetry, compensated or even inverted by the hyperperfusion, was not correlated with the initial score (ns, p = 0.051, r = 0.42) and was weakly correlated to the late score (p = 0.048, r = 0.43). CONCLUSION: The cerebral hemodynamics remain normal in 80% of cases of CPH patients. The presence of CPH does not interfere with the clinical evolution. The initial and late clinical scores were not different compared to those of patients without hyperperfusion. The clinical outcome of the CPH patients cannot be accurately predicted by the interhemispheric asymmetry.

Acetazolamide↗

PubMed1996

Tacrine overcompensates for the decreased blood flow induced by basal forebrain lesion in the rat.

The effects of tacrine on the cerebral blood flow (CBF) were investigated according to an experimental model of the cholinergic hypothesis in rats with unilateral lesion of the substantia innominata (SI). CBF was measured 1-2 weeks following SI lesion with ibotenic acid, using the tissue sampling [14C]iodoantipyrine technique in three groups of lesioned rats infused i.v. with tacrine at 3 or 8 mg kg-1 h-1 or with saline. SI lesioning resulted in moderate, significant blood flow decreases in the parietal, frontal and occipital cortical areas. In the intact hemi-brain, tacrine at a dose of 3 mg kg-1 h-1 had no significant effect, but at 8 mg kg-1 h-1 tacrine increased the blood flow in most of the cortical and subcortical regions investigated. The increases ranged from 21% (hypothalamus) to 101% (parietal cortex) compared with controls. Tacrine had greater effects in the lesioned hemisphere, even at the dose of 3 mg kg-1 h-1. The flow increases in the frontal or parietal cortex of the lesioned hemisphere were 1.5-3.6 times greater than in the intact hemisphere. Thus, in contrast to what was expected, tacrine overcompensates for the cerebrovascular effects of SI lesions.

Animals↗

PubMed1996

Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to somatosensory stimulation.

Whether nitric oxide (NO) mediates--or not--the local cerebral blood flow (CBF) increases occurring during functional brain activation is still a controversial issue. In the present study, we sought to determine whether neuronal NO synthase is involved in the cerebrovascular response to activation of the trigeminal pathway in the rat. Local CBF was measured using the autoradiographic [14C]iodoantipyrine technique in control alpha-chloralose anesthetized rats and 30 min following administration of 7-nitroindazole (7-NI), an inhibitor of the neuronal NO synthase. Unilateral whiskers stroking increased local CBF in all six regions of the trigeminal pathway. Under 7-NI, CBF was slightly decreased and the vasodilatatory response to whisker stimulation was unaltered in the four trigeminal nuclei studied. In contrast, no significant vasodilatation was noted in the ventral posteromedial thalamic nucleus and somatosensory cortex. These results suggest that the neuronal NO synthase mediates the hyperemia associated with somatosensory activation in second order relay stations but not in the site of termination of primary afferents.

Animals↗

PubMed1996

Cerebral blood flow velocity response induced by a 70-hPa Valsalva manoeuvre associated with normo- and hypergravity in humans.

Anti-G straining manoeuvres, derived from the Valsalva manoeuvre (VM), are physiological methods for protecting fighter pilots against positive accelerations (+Gz). The aim of this study was to investigate the effects of a standard VM on cerebral haemodynamics, in normo- and hypergravity. In six healthy male volunteers, we investigated the cerebral blood flow velocity response induced by a 10-s, 70-hPa (52.5 mmHg) VM, under normogravity, +2, +3 and +4 Gz acceleration plateaus. Mean blood flow velocity [formula: see text] in middle cerebral artery was monitored by transcranial Doppler velocimetry. In normogravity, no significant variation in [formula: see text] was observed at the onset of VM. After a maximal period of 1.2 s, while VM was sustained, [formula: see text] decreased significantly (P < 0.05). Following the end of the manoeuvre [formula: see text] did not change significantly. When the expiratory pressure had returned to the control value, [formula: see text] was transiently increased (P < 0.05) before returning to control values. During hypergravity, [formula: see text] was significantly decreased at +3 and +4 Gz (P < 0.05) before the onset of VM. While performing VM under +Gz, the main difference compared to the normogravity condition was a significant increase of [formula: see text] (P < 0.05) at the onset of the manoeuvre. Our findings would suggest that when performed under +Gz stress, a 70-hPa VM can transiently improve cerebral haemodynamics. However, when VM is sustained for more than 1.2 s it results in a lasting decrease of cerebral perfusion which may lower +Gz tolerance.

Adult↗

PubMed1996

Differential processes of vascular smooth muscle cell differentiation within elastic and muscular arteries of rats and rabbits: an immunofluorescence study of desmin and vimentin distribution.

Two main populations of smooth muscle cells exist in the arterial media of adult mammals with respect to expression of two intermediate filament proteins: vimentin-positive/desmin-negative cells (V+/D-) and vimentin-positive/desmin-positive ones (V+/D+). However, it is still not understood how this phenotypic diversity is established. Since the proportion and the distribution patterns of the two muscle cell populations depend both on the type of blood vessel and the species examined, the aim of the present study was to determine and to compare their developmental origin in various artery segments from two different species. Using confocal scanning laser microscopy and sections stained by means of immunofluorescence, the distribution patterns of desmin and vimentin were compared in transverse sections of thoracic and abdominal aortas (elastic arteries) and of the femoral artery (muscular artery) of newborn and adult rats (n = 12) and rabbits (n = 12). The comparison of sections labelled with specific antibodies showed the existence of a subpopulation of smooth muscle cells in the aortas, but not in the femoral artery, which expressed desmin in newborns but not in adults. These data suggest that the phenotype of smooth muscle cells in elastic arteries but not in muscular arteries is modulated during development.

Aging↗

PubMed1996

A one-dimensional (proton and phosphorus) and two-dimensional (proton) in vivo NMR spectroscopic study of reversible global cerebral ischemia.

The suitability of two-dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30-min reversible ischemia induced by four-vessel occlusion in the rat. The resulting data were compared with those obtained by one-dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (-73%), beta-ATP (-60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N-acetylaspartate/creatine-phosphocreatine ratio that were not significantly different [-21% (1D) and -32% (2D)]. Similarly, the increases in lactate/creatine-phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (-66%) and an increase in the inositol-choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate-glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (-67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.

Animals↗

PubMed1996

Absence seizures induce a decrease in cerebral blood flow: human and animal data.

Our previous studies on cerebral metabolic activity in genetic absence epilepsy rats from Strasbourg (GAERS) were in favor of decreased functional activity during absences and normal or increased interictal activity. To ascertain that hypothesis, in the present study we performed continuous measurements of CBF in both children with typical absence epilepsy and GAERS, using Doppler ultrasonography and laser-Doppler flowmetry, respectively. CBF fluctuations during absences were recorded in four children between 5 and 6 years of age and 16 adult GAERS. In both children and animals, CBF measured in the middle cerebral artery and cortical capillaries, respectively, significantly decreased by a median value of 20-24% under basal levels during spontaneous absences. In GAERS, CBF levels were continuously decreased during haloperidol-induced absence status epilepticus, while they were not affected by ethosuximide. Conversely, convulsive seizures induced in rats either by kainate or picrotoxin led to a 175-664% increase in CBF levels. In conclusion, the present data show that during spontaneous absences, CBF decreases under basal levels in both cortical capillaries (GAERS) and the middle cerebral artery (children). Moreover, these fluctuations occur in vessels with normal vascular reactivity, are not mediated by changes in PO2, PCO2, or arterial blood pressure, and represent rather a response to reduced metabolic demand.

Animals↗

PubMed1996

[Cerebral cortical blood flow during parabolic maneuvers].

Cerebral cortical blood flow (CBF) was measured in 6 rabbits during parabolic flight maneuvers (20 s of weightlessness). During the first seconds of weightlessness, CBF increased up to 100% when compared with CBF at 1 G. Since this transient increase (5 s) was not modified when propranolol or pentobarbital was given to the animals, one can hypothesize that it was not related to stress.

Animals↗

PubMed1996

Cerebrovascular reactivity: role of endothelium/platelet/leukocyte interactions.

In the last two decades, a tremendous amount of knowledge has been accumulated in various fields of biomedical research that discloses mechanisms of platelet/leukocyte/endothelium interactions. Occupying a strategically important location between circulating blood and underlying tissues, the endothelium effectively modulates both the functional state of the blood cells and the tone of vascular smooth muscle by generating or metabolizing a host of humoral substances. Under normal conditions, the endothelium releases agents with predominantly vasodilator and antiaggregant/anticoagulant activity that prevent thrombotic and angiospastic disorders. However, a variety of pathophysiological stimuli may trigger endothelial reorganization with the expression of different prothrombotic factors and activation of platelets and leukocytes that, combined, leads to blood cell adhesion to the endothelial monolayer, aggregation as thrombi, and the formation of numerous spasmogenic substances. Activation of the blood cells in the vicinity of the endothelium may induce endothelial dysfunction/injury, resulting in impairment of normal endothelial antispasmodic control. Within the microcirculatory bed, intravascular activation of the blood cells leads to scattered microvessel plugging, increased vascular permeability, edema formation, and cytotoxic actions of blood cell-released agents on the underlying tissue. A growing body of evidence suggests that these processes may be involved in pathophysiological cerebrovascular reactions including symptomatic angiospasm following subarachnoid hemorrhage, segmental occlusive constriction in atherosclerotic cerebral arteries, and constrictive vasomotion in microvessels. A perturbation in the delicate equilibrium between blood cells and endothelium in the microcirculation seems to be a factor aggravating ischemic brain damage or even primarily causing focal cerebral ischemia and scattered microinfarctions. Increased predisposition to these pathophysiologic events might influence unfavorably the effects of risk factors such as hypercholesterolemia, hypertension, and diabetes on cerebrovascular morbidity and mortality. Although the importance of blood cell/endothelium imbalance appears to be clear, its pharmacologic regulation is not sufficiently established. Some drugs have been demonstrated to limit platelet and/or leukocyte activity and protect the endothelial defense mechanisms, but the optimal therapeutic strategy has yet to be elaborated.

Animals↗