Biomedical subjects

J Seylaz

Publications and source records attributed to J Seylaz.

At least 19 recordsLinked to original sources

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↗

PubMed1992

Spreading depression induces prolonged reduction of cortical blood flow reactivity in the rat.

The purpose of the present study was to examine the dynamic aspects of the cerebrovascular events occurring during and up to 2 h following cortical spreading depression (CSD) in the rat, using the mass spectrometry technique which enables continuous measurements of the cortical tissue PO2 and PCO2 and repeated blood flow measurements (CoBF) by helium clearance. We mostly sought to determine whether cortical perforation by a stimulation electrode induced long-lasting perturbation of the cortical vasoreactivity to hypercapnia and basal forebrain electrical stimulation. Cortical perforation in the animal under alpha-chloralose anesthesia, chronically implanted with mass spectrometry probes, was associated with biphasic changes in tissue gases. PO2 first briefly decreased (-7.8%) and then strongly increased (+79%) while PCO2 changed in the opposite direction (+7%, -13%) in the ipsilateral frontal cortex. Qualitatively similar changes occurred in the ipsilateral parietal cortex. The CoBF measurements showed a marked vasodilation (131 and 108% in the frontal and parietal cortex, respectively) in parallel with the PO2 increase, followed by a prolonged (60 min), moderate hypoperfusion (maximum -17% at 20 min after CSD). There was a pronounced reduction of vascular reactivity to both hypercapnia (20.3% of the control response) and substantia innominata stimulation (1/6 of the response obtained 80 min later) at 10 min after CSD. Both reactivities progressively recovered in approximately 2 h. Since the issue of CSD in human has become a popular hypothesis for migraine, the reduced cerebrovascular reactivity could constitute the basis of a test for the involvement of CSD in migraine.

Animals↗

PubMed1992

The acute effects of MK-801 on cerebral blood flow and tissue partial pressures of oxygen and carbon dioxide in conscious and alpha-chloralose anaesthetized rats.

The dynamic effects of the non-competitive N-methyl-D-aspartate receptor antagonist, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine] , on cerebral blood flow and tissue partial pressures of oxygen and carbon dioxide were investigated in the striatal and occipital regions of conscious and anaesthetized rats by mass spectrometry. MK-801 (0.5 and 5 mg/kg, i.p.) induced a large increase in the blood flow of both cerebral regions of conscious rats, without significant changes in local tissue partial pressures of oxygen and carbon dioxide. The increase in cerebral blood flow was maximal within 30 min after injection. Its amplitude was independent of the dose of MK-801, but cerebral blood flow remained elevated for up to 4 h after 5 mg/kg MK-801, while it progressively decreased towards its basal level in rats given 0.5 mg/kg MK-801. The amplitude and time-course of the vascular changes were similar in the two cerebral regions studied. The difference in the changes in tissue partial pressure of oxygen induced by MK-801 and by a 6% CO2 inhalation suggests that the MK-801-induced rise in cerebral blood flow in conscious rats is, at least partly, due to an increase in oxidative metabolism. In contrast, MK-801 induced either no changes or decreases in cerebral blood flow in alpha-chloralose-anaesthetized rats. The present results should be taken into account not only to determine the mechanisms by which N-methyl-D-aspartate receptor antagonists may exert their neuroprotective effects but also to further elucidate the sites of action of MK-801 in the central nervous system.

Anesthesia, General↗

PubMed1992

Differential cerebrovascular and metabolic responses in specific neural systems elicited from the centromedian-parafascicular complex.

The effect of electrical stimulation of the centromedian-parafascicular complex on local cerebral blood flow and local cerebral glucose utilization was investigated in anesthetized, paralysed and ventilated rats. Local cerebral blood flow and local cerebral glucose utilization were measured in separate groups of animals using the autoradiographic (14C)iodoantipyrine and (14C)2-deoxyglucose methods, respectively. Because of the well-established centromedian-parafascicular complex neuroanatomical connections, three functional neuronal systems were analysed and compared: the extrapyramidal motor system the limbic system and the reticular formation, also known as the ascending activating system. Cortical regions not included in the limbic system were considered separately. The validity of comparisons between changes in local cerebral blood flow and local cerebral glucose utilization across the brain was verified by assessing the reactivity and stability of the cortical blood flow during long-term centromedian-parafascicular complex stimulation. Centromedian-parafascicular complex stimulation elicited a marked but heterogeneous increase in local cerebral blood flow in 50 of the 52 cerebral structures measured. The most pronounced increases were seen in the lateral habenular nucleus (331 +/- 30% of control), the zona incerta (400 +/- 55%), the mesencephalic reticular formation (415 +/- 122%) and the parietal cortex (211 +/- 35%). In contrast, local cerebral glucose utilization remained statistically unchanged (P greater than 0.05) in 28 of these 50 individual brain regions during centromedian-parafascicular complex stimulation. The most pronounced increases in local cerebral glucose utilization were seen in the zona incerta (123 +/- 28%) and the mesencephalic reticular formation (193 +/- 26%). Local cerebral blood flow and local cerebral glucose utilization were linearly related in unstimulated controls, considering either all brain regions taken as a whole or the three systems separately. The significant increase in the slopes of the regression line between local cerebral blood flow and local cerebral glucose utilization for the reticular formation and the limbic system during centromedian-parafascicular complex stimulation indicates, however, that the coupling mechanisms for these systems, but not for the extrapyramidal motor system, were reset. The local cerebral blood flow to local cerebral glucose utilization ratio was heterogeneous in controls and differentially increased during centromedian-parafascicular complex stimulation, being markedly pronounced in the parietal cortex and in the reticular formation. We conclude that these results, for the first time, provide evidence that, the functionally well-defined neural networks may have different mechanisms whereby changes in vascular and metabolic demands are regulated.

Anesthesia↗

PubMed1992

Rapid autoregulation of cerebral blood flow: a laser-Doppler flowmetry study.

The mechanisms underlying autoregulation of CBF were studied in 19 rabbits using laser-Doppler flowmetry. A cranial plexiglas window was chronically inserted in the skull with dental cement under general anesthesia. The animals then were reanesthetized 5-7 days later and subjected to aortic bleeding while CBF was measured with the probe placed on the window. In the first set of experiments, MABP was decreased (from 90 to 30 mm Hg) and was maintained constant for 1 min. During the first seconds, CBF followed the steep decrease of MABP. Then, CBF increased and reached a plateau within 3-13 s, depending on the severity of hypotension. Hyperemia occurred when blood was restored, and the CBF recovered from this posthypotensive hyperemia with a rapid phase (within 2 s) and a slow phase (total recovery within 1 min). The lower limit of autoregulation was found to be 40 mm Hg. An increase in CBF due to papaverine showed that vasodilation was not maximal below this limit. In the second set of experiments, the rabbits were subjected to four episodes of hypotension at 40 mm Hg each but of different durations (from 2-3 to 60 s). The posthypotensive hyperemia was not influenced by the duration of hypotension, but the time of the total recovery phase increased with the duration of hypotension. We conclude that there exist rapid adaptive mechanisms leading to autoregulation and that the vasodilation is not dependent upon the duration of hypotension.

Animals↗

PubMed1992

Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat.

Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with alpha-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical (frontal, parietal and occipital) lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate, for the first time, that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome.

Animals↗

PubMed1992

Muscarinic binding of pial vessels and arachnoid membrane.

The muscarinic sites in arachnoid and pial vessels were compared by analysis of the binding of quinuclidinyl benzilate (QNB) to membrane preparations. Saturation analysis indicated that the process was saturable, high affinity, and related to protein concentration in both structures. Although the affinities in the two structures [KD = 0.039 (arachnoid) and 0.097 nM (pial vessels)] were similar, the arachnoid had approximately 10-fold more binding sites (Bmax = 2,100 fmol/mg of protein) than the pial vessels (Bmax = 250 fmol/mg of protein). This difference was found in both bovine and porcine fractions. Pharmacological analysis of [3H]QNB displacement by muscarinic and nonmuscarinic ligands gave the typical pattern of muscarinic receptors in both structures. Inhibition of binding to pial vessels by the M1 antagonist pirenzepine revealed only one low-affinity site (Ki = 7.8 x 10(-7) M), whereas, the arachnoid had a small proportion (21%) of high-affinity sites (Ki = 2.2 x 10(-9) M) associated with low-affinity sites (Ki = 5.50 x 10(-7) M). It is concluded that muscarinic-mediated effects that do not involve the M1 subtype are induced in bovine pial vessels by a relatively low concentration of binding sites. The high content of muscarinic binding sites and their diversity in the arachnoid suggest a functional role for muscarinic cholinergic receptors in this structure.

Animals↗

PubMed1992

Carbachol induces granular cell exocytosis and serotonin release in rabbit cerebral arteries.

Previously, we reported that rabbit cerebral arteries contain mast cells that frequently establish close contacts with parasympathetic-like nerve fibers. Here we have examined the possible function of this link by comparing the effects of carbachol and compound 48/80 on mast cell morphology and on the serotonin (5-HT) and histamine content of these arteries. In vivo, 2 micrograms/min of compound 48/80 or 1 micrograms/min of carbachol was infused for 30 min into one internal carotid artery of pentobarbital anesthetized rabbits, the contralateral artery being infused with vehicle. In vitro, the action of 10(-6) M carbachol was tested on isolated middle cerebral artery trees (MCAs) in the presence or absence of 10(-7) M atropine. The effects of carbachol were also tested in vitro on sympathectomized arteries. The 5-HT and histamine contents of all MCAs were measured by radioenzymatic assay, and fragments were prepared for electron microscopy. No histamine was detectable in any artery studied. The 5-HT content of arteries from control animals and those perfused with vehicle (in vivo) or incubated in the physiological solution (in vitro) was 250-300 pmol/mg protein. Both compound 48/80 and carbachol reduced this amount by approximately 50% and induced a marked degranulation of mast cells. Both secretion and degranulation were dramatically blocked in vitro by atropine. No difference in the 5-HT content was observed between intact and sympathectomized arteries under any condition. We conclude that a large proportion of rabbit cerebrovascular 5-HT is stored in mast cells and that cholinergic nerve activation could theoretically release this pool by acting on mast cell muscarinic receptors.

Animals↗

PubMed1992

Effect of MK-801 on focal brain infarction in normotensive and hypertensive rats.

The effects of the noncompetitive N-methyl-D-aspartate antagonist MK-801 on infarct size and systemic variables after middle cerebral artery occlusion in spontaneously hypertensive and Fischer-344 rats were investigated. Two doses (0.5 and 5 mg/kg) administered before the induction of ischemia were studied. MK-801 significantly reduced the neocortical volume of infarction (by about 32% at both doses) in Fischer-344 rats and had no neuroprotective effects in the striatum. In contrast, MK-801 had no significant influence on either cortical or striatal infarcted volume in spontaneously hypertensive rats. The reduction or lack of MK-801-induced neuroprotection in spontaneously hypertensive rats, as compared with Fischer-344 rats, could be attributed to a reduced collateral supply in the marginal area due to difference in the morphology of the pial anastomoses and/or in the effects of ischemia and treatment on arterial pressure. The results may have major clinical implications since a great proportion of human strokes are associated with hypertension.

Animals↗

PubMed1992

Early changes in rabbit cerebral artery reactivity after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage frequently leads to long-term cerebral artery narrowing called vasospasm. Very early changes in cerebral arteries have not been studied extensively and may be critical for the later pathological developments. We therefore determined what changes in the reactivity of cerebral arteries could be observed after 10 minutes' or 24 hours' contact with subarachnoid blood. METHODS: Ten minutes or 24 hours after the injection of blood or physiological solution (sham hemorrhage) into the cisterna magna of anesthetized rabbits or no injection (control rabbits), segments of the middle cerebral, basilar, and vertebral arteries were removed for conventional in vitro tension measurements. Concentration-response curves to four endogenous constrictors likely to be released after hemorrhage were obtained, and the maximum relaxation to acetylcholine was determined. RESULTS: There were no significant differences between the sham hemorrhage and control groups. Compared with control rabbits, treated animals showed increased reactivity to uridine triphosphate in the basilar and vertebral arteries at 10 minutes but not at 24 hours, whereas reactivity was increased in the middle cerebral artery only at 24 hours. Reactivity to serotonin was greatly increased in all arteries at both latencies (up to 2.7 times). Reactivity to noradrenaline was unchanged in the basilar and vertebral arteries at 10 minutes; reactivity in both the basilar and middle cerebral arteries was increased at 24 hours, which is compatible with denervation supersensitivity. There were only minor changes in the reactivity to histamine, and only at 10 minutes. Relaxation to acetylcholine was increased for the middle cerebral artery at 10 minutes but otherwise was not significantly changed. CONCLUSIONS: Reactivity to uridine triphosphate, serotonin, and noradrenaline greatly increases by 10 minutes to 24 hours after subarachnoid hemorrhage, and this increase is not owing to the mechanical effects of intracranial hypertension, nor is it related to impaired endothelium-dependent relaxation. It is suggested that these and other spasmogens cause excessive muscular calcium loading with a very rapid onset after subarachnoid hemorrhage.

Animals↗

PubMed1992

Cerebral vasodilation after the thermocoagulation of the trigeminal ganglion in humans.

The resulting changes in the regional cerebral blood flow of 18 patients suffering from idiopathic trigeminal neuralgia and treated by selective thermocoagulation of the trigeminal ganglion were measured by xenon-133 emission tomography. One hour after thermal stimulation, there was an asymmetric increase (P < 0.05) in cerebral blood flow, with a 14.7% mean increase in the ipsilateral cerebral hemisphere (P < 0.001) and a 12.7% mean increase in the contralateral side (P < 0.01). The increase in regional cerebral blood flow was not uniform but was most marked in the ipsilateral middle cerebral artery territory (P < 0.001). There was a slight decrease in cerebellar blood flow, but the reduction in the ipsilateral cerebellar lobe was less than that in the contralateral lobe (P < 0.01). The topography of the most significant changes coincided with that of the innervation of the cerebral vessels by the trigeminal nerve. Several mechanisms are involved in the increase in regional cerebral blood flow, including overall nonspecific activation of the central nervous system and local mechanisms associated with the trigeminal-vascular system.

Adult↗

PubMed1991

Effects of dorsal raphe stimulation on cerebral glucose utilization in the anaesthetized rat.

The aim of this study was to determine the effects of electrical stimulation of the dorsal raphe nucleus on local cerebral glucose utilization (LCGU) in the alpha-chloralose anaesthetized rat. Activation of the dorsal raphe nucleus effected significant increases in LCGU, ranging from 13 to 52% in 8 brain structures out of 33 investigated. Increases were restricted to extrapyramidal and limbic non-specific areas, and no modifications were observed in cortical areas. The comparison with our previous results, showing that a similar raphe activation induced a global decrease in local cerebral blood flow, suggests that the ascending serotonergic system may be of importance in the regulation of the cerebral circulation.

Anesthesia↗

PubMed1991

Hypercapnia and stimulation of the substantia innominata increase rat frontal cortical blood flow by different cholinergic mechanisms.

This study was designed to further investigate in the rat how the cerebrovascular response to excitation of the projections from the substantia innominata (SI) to the frontal cerebral cortex was mediated. Local cortical blood flow (CoBF) (by helium clearance) and tissue gas partial pressures (pO2, pCO2) (indices of energy metabolic activity) were measured in the frontal cortex in unanesthetized adult Fischer rats in response to electrical stimulation of the SI and, for comparison, in hypercapnic conditions. SI stimulation and hypercapnia increased CoBF to a similar extent (+92% and +106%, respectively). Differences between the changes in tissue gas partial pressures under hypercapnia and SI stimulation suggest that different patterns of flow-metabolism coupling prevail in the mechanisms underlying the two cerebrovascular responses. Cortical pCO2 increased under hypercapnia, but decreased during SI stimulation, indicating that a 'vascular' mechanism (i.e. independent of energy metabolism activation) is at least partly responsible for the flow increase in the latter condition. However, cortical pO2 rose more under hypercapnia than during SI stimulation, suggesting that oxygen consumption, and hence energy metabolism, was increased in the latter case. The ability of the acetylcholine esterase inhibitor physostigmine and the muscarinic receptor antagonist scopolamine to modulate the responses was quantified. In both experimental conditions, CoBF changes were potentiated by 0.15 mg/kg/h physostigmine (by factors of about 2). In contrast, 1 mg/kg scopolamine reduced by 65% the frontal CoBF response elicited by SI stimulation but was without effect on the response to hypercapnia. Thus, although a cholinergic mechanism may be implicated in both responses, activation of muscarinic receptors appears to occur when the stimulation originates from the SI but not from the hypercapnia.

Animals↗

PubMed1991

Metabolic effects of kynurenate during reversible forebrain ischemia studied by in vivo 31P-nuclear magnetic resonance spectroscopy.

The metabolic effects of kynurenate, an endogenous excitatory amino acid antagonist, were studied by in vivo 31P-NMR spectroscopy before, during and after reversible forebrain ischemia in the rat. Kynurenate had no effect on cerebral metabolism before ischemia. During a 30-min ischemia, kynurenate protected against the decrease in phosphocreatine (up to -55 +/- 3% vs -73 +/- 3% in the reference group) and the increase in inorganic phosphate (up to +479 +/- 39% vs +805 +/- 66%), whereas there was no statistical difference in the decrease in intracellular pH (up to 6.37 +/- 0.05 vs 6.30 +/- 0.03) and ATP (up to -60 +/- 3% vs -60 +/- 7%). The recovery of PCr, Pi, and pHi to control levels during recirculation was faster in the treated group than in the reference group, whereas the time course of ATP recovery was similar in both groups. We conclude that kynurenate protects against neuronal loss, as previously reported, by mechanisms other than metabolic protection.

Adenosine Diphosphate↗

PubMed1991

Focal cerebral ischemia in chronic hypertension: no protection by (R)-phenylisopropyladenosine.

The effects of the adenosine agonist, (R)-phenylisopropyladenosine on focal cerebral ischemia induced by middle cerebral artery occlusion were investigated in spontaneously hypertensive rats. The drug was given 30 min before occlusion and each hour thereafter for 6 h. The neurological status of the rats was estimated 2, 24 and 48 h after occlusion. Infarct volumes were measured 48 h after occlusion (Cresyl violet-stained sections). (R)-Phenylisopropyladenosine did not significantly reduce infarct size, nor did it modify the neurological score. As there is considerable evidence of the neuroprotective effects of adenosine in normotensive rats, the present results may be due to a more abrupt reduction in cerebral blood flow in the territory surrounding the ischemic core, where neuroprotection could be expected, in the spontaneously hypertensive rat strain. Consequently, neuroprotection may be more difficult when focal cerebral ischemia is associated with hypertension.

Animals↗