Biomedical subjects

J Seylaz

Publications and source records attributed to J Seylaz.

At least 73 records · Page 4Linked to original sources

PubMed1994

Spreading depression reversibly impairs autoregulation of cortical blood flow.

The experiment examines whether the mechanisms responsible for the autoregulation of cerebral blood flow (CBF) in response to hypotension were affected during the initial phase of cortical spreading depression (CSD). CSD was induced by a cortical pinprick in anesthetized rabbits, and CBF was measured by laser-Doppler flowmetry through a chronically implanted Plexiglas window. The reactivity to CO2 and papaverine was also studied before and after CSD. Fifteen minutes after CSD, autoregulatory vasodilation was reduced (P < 0.01). This impairment was reversible, since the autoregulatory response was restored 35 min after CSD. The time course of the reactivity to papaverine after CSD paralleled the autoregulatory response, with a significant correlation between the two reactivities (r = 0.47; P < 0.01). Conversely, the reactivity to CO2 was significantly reduced after CSD (P < 0.001) and remained affected for at least 95 min. We conclude that the mechanisms underlying autoregulation are transiently disturbed by CSD and that these mechanisms are not mediated by an accumulation of CO2 but seem instead to be related to an increase in adenosine 3',5'-cyclic monophosphate concentration.

Animals↗

PubMed1994

Substance P, calcitonin gene-related peptide, and capsaicin release serotonin from cerebrovascular mast cells.

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.

Animals↗

PubMed1994

Response of human cerebral blood flow to +Gz accelerations.

Intolerance symptoms associated with high sustained +Gz (head to foot) accelerations are attributed to lack of cerebral perfusion. To determine the response of cerebral circulation to +Gz stress, cerebral blood flow (CBF) was measured in humans with the transcranial Doppler method while cephalic arterial blood pressure was calculated simultaneously using a photoplethysmographic technique. Nine volunteers performed four randomized centrifuge runs at +2 to +5 Gz with a 0.4-G/s onset rate for 30 s. Compared with the control values, for +2-, +3-, +4-, and +5-Gz profiles, CBF was reduced by 19 +/- 7, 26 +/- 8, 49 +/- 26, and 61 +/- 29% (SD), respectively, at the end of the onset and by 18 +/- 4, 21 +/- 11, 27 +/- 7, and 47 +/- 29%, respectively, in the last 20 s of the plateau of acceleration. At the end of the onset and during the plateau of +Gz acceleration, CBF was less reduced than cephalic arterial blood pressure, suggesting that some mechanisms would occur to maintain cerebral perfusion under +Gz stress. These protective mechanisms are likely due to a siphon effect and/or an autoregulatory compensation.

Acceleration↗

PubMed1994

Cortical blood flow and +Gz acceleration in conscious rabbits.

We examined whether superficial cortical blood flow (CBF) of nonanesthetized rabbits (n = 11) is affected by gravitational (G) stress. Blood flow was measured by laser-Doppler flowmetry through a chronic Plexiglas window implanted over the parietal cortex. Mean arterial blood pressure (MABP) was recorded via an aortic catheter with the pressure transducer situated at the level of the head. The electrocorticogram (ECoG) was also studied in seven rabbits. The animals were exposed to tail-to-head acceleration [6, 10, 15, and 20 G acceleration (Gz) for 1 min]. MABP fell with increasing acceleration (regression line equation: MABP = -7.0 Gz + 129.1; P < 0.001, r = 0.85), whereas CBF was statistically either not different from or greater than control. In one rabbit exposed to 20 Gz, high voltage and slow waves were observed on the ECoG and these changes were preceded by a decrease in CBF to 66% of control. We conclude that the stress and the siphon effect may account for the maintenance of elevated CBF despite low or negative MABP until the occurrence of vascular collapse that induces loss of consciousness.

Acceleration↗

PubMed1994

Time course of variations in rabbit cerebrospinal fluid levels of calcitonin gene-related peptide- and substance P-like immunoreactivity in experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cerebral vasospasm after subarachnoid hemorrhage may result partially from the imbalance between vasodilator and vasoconstrictor factors. The vasodilator peptides substance P and calcitonin gene-related peptide contained in the trigeminovascular system are involved in the vasomotor phenomenon occurring after subarachnoid hemorrhage. The delayed arterial narrowing may reflect the time course of the release of these peptides. Therefore, we followed the time course of the changes in cerebrospinal fluid immunoreactivity of substance P and calcitonin gene-related peptide in a model of experimental subarachnoid hemorrhage. METHODS: Cerebrospinal fluid samples were taken in the basal state and at 30 minutes, 24 hours, and 3 days after a single injection of 1 mL autologous arterial blood into the cisterna magna of rabbits using a percutaneous suboccipital route. Substance P-like and calcitonin gene-related peptide-like immunoreactivities were determined in centrifuged cerebrospinal fluid and plasma by use of enzyme immunoassay. RESULTS: Early (30 minutes) after induced subarachnoid hemorrhage, there was a large increase in cerebrospinal fluid substance P-like immunoreactivity (P < .01) and calcitonin gene-related peptide-like immunoreactivity (P < .01). Arterial and hemorrhagic cerebrospinal fluid levels of substance P-like immunoreactivity were different (P < .03), indicating that the increased cerebrospinal fluid level did not result only from the blood contamination. Twenty-four hours after induced subarachnoid hemorrhage, the immunoreactivities of substance P and calcitonin gene-related peptide remained significantly higher than the basal level (P < .01). At day 3, both immunoreactivities had decreased to a level nonsignificantly different from the basal level. CONCLUSIONS: The early high values of the cerebrospinal fluid immunoreactivities for substance P and calcitonin gene-related peptide, apart from the contamination by arterial blood, probably resulted from the depletion of neurotransmitter peptides from the trigeminovascular fibers.

Animals↗

PubMed1994

Leukocyte-induced acute endothelial dysfunction in middle cerebral artery in rabbits. Response to aggregating platelets.

BACKGROUND AND PURPOSE: Recent evidence suggests a possible role for leukocytes in angiospastic reactions of large cerebral arteries. This study examined the effect of activation of endogenous circulating leukocytes on endothelium-dependent relaxation in the middle cerebral artery in rabbits. METHODS: Leukocytes were activated by rapid injection of either 40 micrograms/kg phorbol 12-myristate 13-acetate, or 0.2 mg/kg N-formyl-methionyl-leucylphenylalanine into the left carotid artery. Control rabbits received an equal volume of vehicle. Concentration-dependent isometric tension responses of the left and right middle cerebral artery to the dilators acetylcholine, ADP, sodium nitroprusside, or calcium ionophore (A23187), as well as to aggregating platelets, were compared in vitro in control animals and in animals killed 10 minutes after the injection of leukocyte activators in normal and leukocyte-depleted rabbits. RESULTS: In the control animals there was no significant difference in the reactivity of the left and right middle cerebral arteries. The injection of the leukocyte activators led to enhanced contractile responses to aggregating platelets and a significant reduction in the endothelium-dependent relaxation in response to acetylcholine, ADP, and A23187 in the left middle cerebral artery (the injected side), whereas the effect of an endothelium-independent dilator sodium nitroprusside remained unchanged. In leukocyte-depleted rabbits the injection of either of the leukocyte activators used did not induce significant changes in the reactivity of the left middle cerebral artery. CONCLUSIONS: Intravascular leukocyte activation appears to induce an acute disturbance of the endothelium-dependent relaxation. Under these conditions, platelet activation might result in marked angiospastic reactions of large cerebral arteries.

Animals↗

PubMed1993

Effect of nimodipine on the autoregulation of cerebral blood flow studied by laser-Doppler flowmetry.

The present work examines whether nimodipine impairs autoregulation of CBF during hypotension. The CBF of 16 anesthetized rabbits was measured with a laser-Doppler flowmetry probe placed on the external surface of a plexiglas window, chronically inserted in the skull. Autoregulation was triggered by aortic bleeding. First, the effects of three doses of nimodipine (1, 3 and 10 micrograms/kg) and the solvent were studied in 10 rabbits in which MABP was maintained at 50 mmHg for one minute. Second, 10 micrograms/kg i.v. nimodipine was administered to 6 rabbits in which MABP was kept at 30 mmHg for one minute. Before bleeding, the 10 micrograms/kg dose significantly decreased MABP (from 96 +/- 11 mmHg to 81 +/- 11 mmHg, P < 0.01) and increased CBF (from 104 +/- 20% to 147 +/- 25%, P < 0.01) as compared to the solvent. In the first set of experiments, only the 10 micrograms/kg dose suppressed the autoregulatory vasodilation, but CBF was not different from control (84 +/- 17% versus 87 +/- 12%), probably because of the previous induced vasodilation. In the second set of experiments, active vasodilation occurred and the CBF during hypotension was not different from control (72 +/- 26% versus 65 +/- 11%). We conclude that under nimodipine the triggering of the active autoregulatory vasodilation is dependent on both the severity of hypotension and the previous nimodipine-induced vasodilation.

Animals↗

PubMed1993

Cerebrovascular and metabolic uncoupling in the caudate-putamen following unilateral lesion of the mesencephalic dopaminergic neurons in the rat.

Changes in local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) were assessed in dopaminergic primary target areas in the rat 6 weeks after unilateral lesion of dopaminergic neurons within the substantia nigra pars compacta (SNc) and adjacent ventrotegmental area (VTA) using 6-hydroxydopamine (6-OHDA). lCBF and lCGU were determined using the autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose method. Dopaminergic deafferentation provoked a marked unilateral lCBF decrease in the dorso-lateral portion of the rostral caudate-putamen. The decrease in lCBF was not associated with significant changes in glucose metabolism. Thus, lesions of dopaminergic afferents to the caudate-putamen appear to provoke a sustained decrease in basal blood flow with unchanged local metabolic activity.

Afferent Pathways↗

PubMed1993

Adenosine modulation of amino acid release in rat hippocampus during ischemia and veratridine depolarization.

This study was undertaken to determine whether endogenous adenosine modulates 'in vivo' neurotransmitter amino acid release via its presynaptic receptors. Two conditions were compared: neuronal depolarization by local infusion of veratridine (600 microM), and transient global ischemia by four-vessel occlusion. Both stimuli were applied for 20 min. Extracellular amino acid (glutamate, taurine/GABA, glycine) variations in concentration were determined in the rat hippocampus by microdialysis and HPLC. Modulation of adenosine receptor activity was objectified by continuous local infusion of an adenosine agonist (R-phenylisopropyladenosine R-PIA) or an antagonist (theophylline), starting one hour before stimulation of amino acid release. R-PIA (100 microM) significantly decreased the glutamate release (50%) evoked by veratridine, whereas it did not significantly modify the ischemia-induced glutamate release. In contrast, theophylline did not significantly affect veratridine-induced glutamate release, but it significantly potentiated glutamate efflux (400%) under ischemic conditions. Neither treatment altered the release of the other amino acids. These data suggest that endogenous adenosine appearing in the extracellular space during veratridine-induced depolarization cannot control glutamate release. In contrast, ischemia-induced glutamate release was strongly inhibited by the concomitant increase in extracellular adenosine.

Adenosine↗

PubMed1993

The cerebrovascular effects of physostigmine are not mediated through the substantia innominata.

This study sought to determine whether the cortical cholinergic projections from Meynert's nucleus are actually the target of the cholinesterase inhibitor physostigmine, which presents the ability to increase cortical blood flow. To this aim, the multiregional cerebrovascular effects of physostigmine in rats with and without lesion of the substantia innominata (SI), the equivalent of Meynert's nucleus of primates, were investigated. Unilateral SI lesions were made using ibotenic acid in three groups of rats. Four to 11 days later, the cortical choline acetyltransferase (ChAT) activity was measured in one group to assess the efficacy of the lesion. In the two other groups, the regional cerebral blood flow was measured using the [14C]iodoantipyrine technique, under physostigmine (0.2 mg/kg/h iv) or control conditions. SI lesion induced 27-59% fall in cortical ChAT activity in the ipsilateral hemisphere with the frontal area most affected. Despite these large biochemical differences, the lesion had little cerebrovascular effects. Side-to-side blood flow differences did not exceed 11% and did not strictly overlap the ChAT depletion. Physostigmine increased flow (38-66%) in all cortical areas, with no frontal predominance. Despite these considerable vasodilations, there were no significant differences between the lesioned and the intact hemisphere, nor any significant interaction between physostigmine and SI lesion. Thus, physostigmine does not actually activate the SI neuron terminals. This result suggests that cholinesterase inhibitors cannot be used as presynaptic markers of the cholinergic activity of this nucleus and casts doubts on their specificity as enhancement therapeutic agents in Alzheimer's disease.

Animals↗

PubMed1993

Effects of dorsal raphe nucleus stimulation on cerebral blood flow and flow-metabolism coupling in the conscious rat.

In the present study, we have investigated the effects of an activation of the ascending serotonergic pathway on the cerebral blood supply to a number (63) of well-defined neuroanatomical structures. To this end, we have measured the local cerebral blood flow during electrical stimulation of the dorsal raphe nucleus. Measurement of regional blood flow was performed in the conscious rat through the use of the [14C]iodoantipyrine autoradiographic technique. Stimulation of the dorsal raphe nucleus induced increases (> 15% compared to control) in cerebral blood flow in 17 structures of which statistical significance (P < 0.05) was achieved in nine; raphe stimulation significantly decreased flow in three regions. The greatest increases (+71 and +46%) were found in the frontal sensorimotor and posterior parietal cortices. Other increases were noted in relay stations of the extrapyramidal and limbic systems. Stimulation induced a decrease in two regions of the primary auditory system and in the lateral habenular nucleus. These results show that activation of the serotonergic pathway in the conscious rat effects regional cerebral blood flow heterogeneously, differing from the widespread increase in glucose utilization that we previously observed using the same experimental paradigm. Statistical analyses indicated that activation of the dorsal raphe nucleus resulted in a global modification of the flow-metabolism ratio. Moreover, in 19 out of 31 regions analysed, this ratio is significantly altered as compared to control. The dichotomy between raphe-induced changes in flow and glucose-metabolism could be explained by one or both of two hypotheses; firstly there could be a direct serotonergic innervation of cerebral resistance vessels; secondly, during raphe stimulation it could be that glucose use is not the primary determinant of tissue perfusion.

Animals↗

PubMed1993

Increased influence of calcium and nicardipine on rabbit basilar artery reactivity after brief subarachnoid hemorrhage.

We studied the changes in reactivity of basilar arteries immediately after a subarachnoid hemorrhage (SAH) in response to serotonin (5-HT), uridine 5'-triphosphate (UTP), and extracellular Ca2+. Although much evidence suggests that an early phase of vasoconstriction occurs after SAH, no direct data exist on changes in the role of extracellular Ca2+ shortly after in vivo contact with subarachnoid blood. Ten minutes after injection of blood (SAH) or physiologic solution (sham SAH) into the cisterna magna, rabbits were killed and their basilar arteries were removed for isometric tension measurements on 3-mm segments. Responses to UTP, 5-HT, and Ca2+ (with addition of 100 mM K+) were compared between SAH, sham SAH, and control arteries. SAH arteries showed substantially increased responses to all agents as compared with the other two groups. The calcium entry blocker nicardipine (10(-10)-10(-8) M) inhibited all responses to Ca2+ in a concentration-dependent manner; the most sensitive arteries were the SAH arteries. At 10(-9) M nicardipine and 1.5 mM Ca2+, the inhibition attained 52.4% for control, 39.7% for sham SAH, and 70.5% for SAH (p < 0.05, SAH vs. sham SAH). The results suggest that calcium entry into smooth muscle cells is facilitated by SAH, and this might be explained by an increased number of operational calcium channels. This change, in the presence of spasmogens such as the platelet-derived factors we tested, should result in very early large-scale Ca2+ entry, which might contribute to development of the delayed arterial narrowing known as vasospasm which is a major complication of SAH.

Animals↗

PubMed1993

Noncholinergic, nonadrenergic cortical vasodilatation elicited by thalamic centromedian-parafascicular complex.

The centromedian-parafascicular complex (CMPf) of the intralaminar thalamus was stimulated in anesthetized, ventilated rats, and cerebral cortical perfusion was continuously measured using laser Doppler flowmetry. Stimulation led to a frequency- and intensity-dependent increase in cortical perfusion (vasodilatation). The maximum response was seen at a rate of 200/s, and studied at 150 microA, was a 120 +/- 27% (n = 6) increase in flow. The mean time from the initiation of stimulation to a change in the cerebral blood flow measured by laser Doppler flowmeter signal was 800 +/- 100 ms (n = 13). The response to electrical stimulation was not blocked after high spinal cord section. Chemical stimulation of the CMPf neurons by microinjection of carbachol led to a 98 +/- 15% (n = 4) increase in flow. The response to electrical stimulation was not blocked by the muscarinic antagonist scopolamine (1 mg/kg) or by the nicotinic antagonist mecamylamine (4 mg/kg). It was also unaffected by the beta-adrenoceptor antagonist propranolol (1.5 mg/kg). These data add to understanding of the CMPf cerebral vasodilator response by demonstrating a robust stimulus-locked change in cortical perfusion that does not involve a cholinergic or adrenergic mechanism. It is also shown to be frequency and intensity dependent, consistent with a functioning physiological system, and has a rapid onset consistent with a primarily neurally mediated phenomenon. Furthermore, it is elicited by pathways that may possibly be entirely within the central nervous system and is due to activation of cell bodies within the region.

Animals↗

PubMed1993

Abnormal cerebral vasodilation in aneurysmal subarachnoid hemorrhage: use of serial 133Xe cerebral blood flow measurement plus acetazolamide to assess cerebral vasospasm.

A patient with cerebral vasospasm following subarachnoid hemorrhage (SAH) was investigated by serial measurement of cerebral blood flow (CBF) using the xenon-133 emission tomography method. The CBF was measured before and after acetazolamide injection. On Day 2 after SAH, there was early local hyperperfusion in the middle cerebral artery (MCA) territory, ipsilateral to the left posterior communicating artery aneurysm. The regional CBF of this arterial territory decreased slightly after acetazolamide injection, probably because of vasoplegia and the "steal" phenomenon, and thus surgery was delayed. A right hemiplegia with aphasia and disturbed consciousness occurred 4 days later (on Day 6 after SAH) due to arterial vasospasm, despite treatment with a calcium-channel blocker. The initial hyperemia of the left MCA territory was followed by ischemia. The vasodilation induced by acetazolamide administration was significantly subnormal until Day 13, at which time CBF and vasoreactivity amplitude returned to normal and the patient's clinical condition improved. Surgery on Day 14 and outcome were without complication. It is concluded that serial CBF measurements plus acetazolamide injection are useful for monitoring the development of cerebral vasospasm to determine the most appropriate time for aneurysm surgery.

Acetazolamide↗

PubMed1992

Cerebrovascular nerve fibers immunoreactive for tryptophan-5-hydroxylase in the rat: distribution, putative origin and comparison with sympathetic noradrenergic nerves.

The distribution of serotonergic nerves in major basal and isolated small pial arteries (diameter > or = 50 microns) was investigated immunohistochemically using an antibody directed against tryptophan-5-hydroxylase (TPOH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine (5-HT or serotonin), and compared to that of the noradrenergic system labeled for the selective noradrenaline (NA) synthesizing enzyme, dopamine-beta-hydroxylase (DBH). In addition, the possible peripheral and/or central origins of the cerebrovascular serotonergic (TPOH-positive) nerve fibers were examined. Strongly labeled TPOH-immunoreactive (TPOH-I) fiber bundles were observed in major basal arteries and gave rise to small varicose fibers organized in a meshwork pattern. The highest density of TPOH-I fibers was found in the middle cerebral artery followed by the anterior cerebral and the anterior communicating arteries, with a moderate to low density in the internal carotid and the vertebro-basilar trunk. Of the isolated pial arteries, only the larger ones (diameter > 75 microns) were significantly endowed with TPOH-I varicose fibers. However, free floating TPOH-I nerves were observed coursing through the pia-arachnoid membranes and reaching small pial vessels. In contrast, DBH-I nerve fibers were fine and were visualized primarily as numerous varicosities distributed in a circumferential manner around the vessel wall. A very high density of DBH-I varicosities was seen in the rostral part of the circle of Willis, with the internal carotid being the most richly supplied followed by the anterior cerebral and the anterior communicating arteries; comparatively, the middle cerebral artery was moderately innervated. The differences in distribution pattern and density between TPOH-I and DBH-I cerebrovascular fibers clearly suggest that these two innervation systems are not exactly superimposable. Superior cervical ganglionectomy caused an almost complete disappearance of TPOH-I nerves in all vascular segments, with some residual fibers in selected vessels. Lesion of the central serotonergic component with the neurotoxin 5,7-dihydroxytryptamine had virtually no effect on the TPOH-I fibers in the major basal and isolated pial arteries. These results strongly suggest that the serotonergic innervation of major cerebral as well as pial arteries has a prominent peripheral origin closely related to the sympathetic system. Processing of superior cervical ganglion slices for TPOH immunocytochemistry, however, failed to unequivocally detect TPOH-I neurons.

5,7-Dihydroxytryptamine↗

PubMed1992

Effect of two different routes of administration of R-PIA on glutamate release during ischemia.

Considering that adenosine decreases glutamate release from brain slices by stimulating presynaptic A1 receptors, we have attempted to modulate glutamate release in vivo during global ischemia with an agonist (R-phenylisopropyladenosine, R-PIA) of A1 receptors. Extracellular hippocampal glutamate was sampled by microdialysis and measured by HPLC. Conscious rats were submitted to transient global ischemia for 20 min. Ischemia induced a significant increase (10 fold) in extracellular glutamate. R-PIA (20 micrograms/kg) administered i.p. 30 min before ischemia significantly reduced (-64%) glutamate release. Conversely, R-PIA (100 microM) continuously infused through the hippocampal dialysis probe did not significantly modify glutamate efflux. The efficiency of infused R-PIA was evidenced by the decrease (-47%) of glutamate release induced by veratridine depolarization. These results indicate that the depressive action of R-PIA during ischemia results from various effects which are not restricted to a local action on the hippocampus.

Animals↗

PubMed1992

Insulin protects brain tissue against focal ischemia in rats.

The influence of insulin on the infarct volume due to middle cerebral artery (MCA) occlusion was investigated in rats. A small dose of insulin (1 unit/kg) was injected i.p. just after MCA occlusion. The infarct areas were measured by planimetry from brains perfused with 2,3,5-triphenyltetrazolium-chloride (TTC) 48 h after the occlusion. Systemic variables were measured before and at various times after ischemia. The comparison between insulin-treated (n = 14) and control (n = 13) rats provided evidence that insulin significantly reduced the infarct volume due to MCA occlusion. As insulin minimally and transiently decreased blood glucose, the present results suggest that insulin exerts a beneficial effect directly on the central nervous system.

Anesthesia↗

PubMed1992

In vivo identification and monitoring of changes in rat brain glucose by two-dimensional shift-correlated 1H NMR spectroscopy.

Intracerebral glucose resonance was directly detected and resolved in vivo by two-dimensional shift-correlated (COSY) 1H NMR spectroscopy in anesthetized rats (n = 4). The relative changes in brain glucose concentration were measured by volume integration of the alpha-D-glucose cross peak in the 2D COSY spectra. This report demonstrates the possibility of monitoring the variations in cerebral glucose following iv injection of glucose.

Animals↗