Biomedical subjects

J Seylaz

Publications and source records attributed to J Seylaz.

At least 109 records · Page 6Linked to original sources

PubMed1991

[Value of in vivo NMR spectroscopy in the study of cerebral metabolism under inhalation anesthesia].

NMR in vivo spectroscopy is one of the few methods available for non-invasive investigations of cerebral metabolism in animals and humans. 31P and 1H spectroscopy are particularly suitable for monitoring the cerebral energy metabolism by determining the cerebral levels of ATP, ADP, phosphocreatine (PCr), inorganic phosphate (Pi), lactate and intracellular pH (pHi). These techniques also seem to be suitable for studying the effects of anesthetics by directly comparing the anesthetized and unanesthetized states in the same subject. The effects of halothane and isoflurane on the changes elicited in the cerebral energy metabolism by experimental hypercapnia were investigated by in vivo NMR spectroscopy. Halothane was found to aggravate the decrease in PCr attributed to the shift in creatine kinase equilibrium induced by the cerebral acidosis associated to hypercapnia, while the level of cerebral ADP was decreased to a lesser extent than in unanesthetized animals. In contrast isoflurane did not modify the changes in cerebral energy metabolism elicited by hypercapnia except that the decrease in PCr was significantly slowed, suggesting a lower creatine kinase activity. These data indicate that isoflurane and halothane act by two different mechanisms to produce a decrease in oxygen consumption. Halothane could interfere with oxidative metabolism by disturbing ATP metabolism, while isoflurane could decrease oxygen consumption by a general sedative action, slowing both cerebral functional activity and cerebral energy homeostasis.

Anesthesia, Inhalation↗

PubMed1990

Effect of chronic cervical sympathectomy on local cerebral blood flow during limbic seizures in rat.

The vascular changes in the hippocampus and neocortex during kainic acid-induced seizures were investigated in control rats and in rats with chronic, bilateral, cervical sympathectomy. Seizures were induced in unanesthetized, spontaneously breathing rats. The increase in blood flow in the hippocampus of the sympathectomized rats was significantly reduced during the motor seizures, while the reduction in the neocortex was only significant when the increased blood flow was maximal.

Animals↗

PubMed1990

Kynurenate does not reduce infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats.

The effects of the excitatory amino acid receptor antagonist, kynurenate, were investigated in spontaneously hypertensive rats after middle cerebral artery occlusion. Kynurenate did not significantly modify either the infarct volume, measured 48 h after occlusion, or the neurological score. The absence of a neuroprotective effect of kynurenate in this study, which contrasts with results in normotensive rats, is suggested to be due to impaired collateral circulation in spontaneously hypertensive rats.

Animals↗

PubMed1990

Cerebral intracellular pH regulation during hypercapnia in unanesthetized rats: a 31P nuclear magnetic resonance spectroscopy study.

The energy metabolism and the brain intracellular pH regulation under arterial CO2 tensions of 25-90 mm Hg were investigated in unanesthetized spontaneously breathing rats by in vivo phosphorus nuclear magnetic resonance spectroscopy (31P NMR). The 31P brain spectra, recorded with a high resolution spectrometer (AM 400 Brucker), allowed repeated non-invasive measurements of cerebral pH (pHi), phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) levels in 15 rats breathing a gas mixture containing 21% O2, N2, and a varied percentage of CO2. The pHi decreased significantly when the paCO2 was increased by hypercapnia. The percentage of pH regulation, estimated from the linear regression analysis of pHi versus the logarithm of the paCO2 was 78%. This result indicates that spontaneously breathing unanesthetized animals have better pHi regulation under hypercapnia investigated than that estimated for higher levels of hypercapnia in previous studies on unanesthetized animals, suggesting that there is a threshold for this highly efficient regulation. Furthermore, there were no significant correlations between the PCr, ATP and Pi levels and the paCO2 levels during hypercapnia. This indicates that physiological variations of the CO2 tension in the blood, and consequently in the brain parenchyma, have little effect on cerebral energy metabolism in unanesthetized spontaneously breathing animals.

Animals↗

PubMed1990

2D COSY 1H NMR: a new tool for studying in situ brain metabolism in the living animal.

2D COSY 1H NMR with surface coil has been used to resolve and assign cerebral metabolites which had previously been detected but could not be resolved or assigned in situ in the living animal by conventional 1D 1H NMR. A wide range of cerebral metabolites, including alanine, N-acetyl aspartate, aspartate, choline derivatives, creatine/phosphocreatine pool, GABA, glucose, glutamate/glutamine pool, inositol, lactate and taurine were simultaneously resolved and assigned in situ in the whole animal using the 2D COSY correlation graphs. Global irreversible ischemia caused the appearance and the disappearance of cross-peaks in the 2D COSY 1H NMR map, corresponding to increases in alanine, GABA and lactate and glucose depletion.

Animals↗

PubMed1990

Theophylline reduces cerebral hyperaemia and enhances brain damage induced by seizures.

Hippocampal and neocortical blood flows and tissue pO2 were investigated by mass spectrometry in unanaesthetized spontaneously breathing rats during kainic acid-induced seizures to determine whether adenosine is involved in the coupling of cerebral blood flow to metabolism during enhanced metabolic demand. The possible involvement of adenosine in the neuronal damage induced by seizures was also analyzed. The intrinsic effects of theophylline and the duration of the adenosine receptor blockade by this xanthine were first tested in 8 rats. Two groups of rats were then compared: one (n = 6) received kainic acid, and the other (n = 10) theophylline 15 min prior to kainic acid administration. An additional group of 10 rats was taken for classical histology 48 h after kainic acid treatment. Theophylline significantly reduced the hyperaemia observed during seizures, prevented any tissue hyperoxia and enhanced brain damage. This strongly suggests that adenosine is partly responsible for the increase in cerebral blood flow during kainic acid-induced seizures and has neuroprotective properties.

Adenosine↗

PubMed1990

Amine-induced responses of pial and penetrating cerebral arteries: evidence for heterogeneous responses.

Middle cerebral arteries (MCAs) of rabbits were compared with two types of small branches (less than 100-microns outer diameter), penetrating arteries (PAs) and surface arteries (SAs), by determining their mechanical reactivity to several amines and standard contractile agents. Two techniques were employed: (a) measurement of isometric tension of 1-mm rings (MCA, PA, or SA); (b) measurement of perfusion pressure of segments consisting of essentially MCA or essentially PA. Both techniques revealed similar reactivity of the different types of vessel to acetylcholine, i.e., relaxations to a maximum of 52-78%, and similar strong contractile responses to histamine, although the MCA was more sensitive. Under H1 blockade, histamine dilated the PA (both techniques) and the MCA (perfusion technique), but not the SA. Relatively weak contractile responses to serotonin were observed in the MCA (both techniques) and the PA (perfusion technique), but not the SA (isometric tension only); no dilative responses could be elicited. Responses to noradrenaline varied with the vessel considered: The MCA contracted only, whereas the PA weakly contracted or relaxed at basal tone, and many preparations relaxed after precontraction with uridine triphosphate; the SA did not react. Relaxation of precontracted PA by noradrenaline occurred at relatively low concentrations and was antagonized by propranolol at 3 x 10(-7) or 3 x 10(-6) M. These results reveal very significant differences in the segmental reactivity to amines and suggest that noradrenaline released from sympathetic fibers might have opposing actions in the major pial arteries and the smaller penetrating branches.

Acetylcholine↗

PubMed1990

Differential effects of electrical stimulation of the dorsal raphe nucleus and of cervical sympathectomy on serotonin and noradrenaline concentrations in major cerebral arteries and pial vessels in the rat.

The levels of noradrenaline (NA), serotonin (5-HT), and 5-hydroxyindoleacetic acid were measured by HPLC and compared between the large arteries of the circle of Willis and the small pial vessels in the rat, following either electrical stimulation of the dorsal raphe nucleus or bilateral superior cervical ganglionectomy. With electrical stimulation, the 5-HT concentrations were reduced (-48%) in the small pial vessels, but were unchanged in the major cerebral arteries. NA concentrations were dramatically reduced following cervical sympathectomy in the large arteries (-77%), though the reduction was less pronounced (-34%) in the small vessels. Sympathectomy caused a significant decrease in the 5-HT concentration of the major cerebral arteries (-33%), but was without effect on the 5-HT levels of the small pial vessels. These results show that an appreciable fraction of the perivascular 5-HT measured in the small pial and the large cerebral arteries originates from different sources.

Animals↗

PubMed1990

Effects of methylene blue on hypoxic cerebral vasodilatation in the rabbit.

The present studies were conducted to examine the role of cerebrovascular guanylate cyclase in hypoxic cerebral vasodilatation. In arteries mounted in vitro for measurements of isometric tension, 20 min of hypoxia (bath oxygen partial pressure, approximately 15 Torr) significantly increased cyclic GMP levels from 16 to 32, from 15 to 25 and from 20 to 38 pmol/g in rabbit common carotid, internal carotid and basilar arteries. These increases were blocked either by pretreatment with 3 microM methylene blue, or by removal of the vascular endothelium. Methylene blue also significantly delayed hypoxic relaxation in the basilar and internal carotid arteries, and blocked transient hypoxic vasoconstriction in the common carotid. Together, these in vitro results demonstrate that vascular cytosolic guanylate cyclase participates in an endothelium-dependent manner in the direct effects of hypoxia on cerebral arteries, and that the nature of this participation varies significantly between arteries. When methylene blue (20 mg/kg) was administered in vivo, however, it had no effect on the magnitude of hypoxic cerebral vasodilatation as determined by both local (mass spectrometry) and global (venous outflow) methods of blood flow measurement. This latter finding suggests that: 1) large and small cerebral arteries may differ significantly in terms of either endothelial function or sensitivity to methylene blue; or 2) feedback regulation of other mechanisms of hypoxic cerebral vasodilatation compensate for the effects of guanylate cyclase inhibition. Additional experiments using other inhibitors of cytosolic guanylate cyclase and/or vessels isolated from the cerebral microcirculation will be necessary to distinguish between these possibilities.

Animals↗

PubMed1989

Cortical blood flow increases induced by stimulation of the substantia innominata in the unanesthetized rat.

The possible implication of projections from the substantia innominata (SI) to the cerebral cortex in the control of local cortical blood flow (CoBF) was studied in adult Fischer rats. Local blood flow (by helium clearance) and tissue gas partial pressures (pO2, pCO2) as metabolic indices, were measured in the frontal and parietal cortices in unanesthetized animals via chronically implanted probes connected to a mass spectrometer. Stimulating electrodes, also implanted chronically, were placed in the region of the SI. Out of 37 correctly located sites, 28 gave rise to cerebrovascular responses without significant hypertension or agitation. Both frontal (+114%) and parietal CoBF (+28%) increased significantly during ipsilateral 50 microA stimulation, but did not further significantly increase at 100 microA. Contralateral stimulation induced only small, non-significant effects. SI stimulation simultaneously increased cortical pO2 and decreased cortical pCO2, significantly more so in the frontal compared to the parietal cortex, and ipsilaterally compared to contralaterally. Both the CoBF and the tissue gas changes induced by SI stimulation were strongly potentiated by infusion of 0.15 mg/kg/h of the cholinomimetic agent physostigmine. The electrocorticogram (ECoG) was not systematically activated during the SI stimulation. The evidence presented favors a role for the cholinergic projections of the SI in control of CoBF (particularly frontal cortex), especially since the flow changes observed showed no obvious dependence on changes in local pCO2 or on paCO2, and could not be attributed to hypertension or behavioral changes.

Animals↗

PubMed1989

Role of adenosine in cerebral hypoxic hyperemia in the unanesthetized rabbit.

The present study was undertaken to determine the importance of adenosine in the cerebrovascular response to hypoxia. The mass spectrometry method was used to investigate local blood flow, tissue pO2 and pCO2 in 3 cerebral structures: caudate nucleus (n = 8), thalamus (n = 5) and hippocampus (n = 5) in unanesthetized, spontaneously breathing rabbits. After having tested the reproducibility of the hypoxic response each animal was exposed twice to moderate hypoxia. I.v. theophylline (10 mg/kg) was administered between the first and second exposures to hypoxia. The principal finding is that in each cerebral region, the vasodilatation induced by hypoxia was significantly decreased by pretreatment with theophylline despite the low theophylline dose used. It is concluded that adenosine is partly responsible for the cerebral vasodilatation observed during hypoxia. Several other mechanisms possibly involved in this cerebrovascular response are discussed.

Adenosine↗

PubMed1989

Effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow in the rat.

We have studied the effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow (LCBF), as assessed by the quantitative [14C]-iodoantipyrine autoradiographic technique. Stimulation of the dorsal raphe nucleus in the alpha-chloralose anesthetized rat caused a significant decrease in LCBF, ranging from -13 to -26% in 24 brain structures out of 33 investigated. The most pronounced decreases (-23 to -26%) were observed in the accumbens, amygdaloid, interpeduncular nuclei and in the median raphe nucleus, limbic system relays. The decreases also concerned cortical regions and the extrapyramidal system. These results indicate that activation of ascending serotonergic system produces a vasoconstriction and that the dorsal raphe nucleus has a widespread modulatory influence on the cerebral circulation.

Animals↗

PubMed1988

Effect of monoamine oxidase inhibition on the regional cerebral blood flow response to circulating noradrenaline.

The effect of an acute i.v. infusion of noradrenaline (NA) on regional cerebral blood flow (rCBF) was investigated in the awake rat using [14C]iodoantipyrine as diffusible tracer. The contribution of vascular monoamine oxidase (MAO) to the efficiency of the enzymatic blood-brain barrier (BBB) to catecholamines was assessed by measuring the multiregional cerebrovascular response to circulating NA given alone or after i.v. administration of the monoamine oxidase inhibitor, clorgyline. Since i.v. infusion of NA elevates blood pressure, the influence of NA on the cerebrovascular bed was first studied by determining the relationship between rCBF and the mean arterial pressure (MAP). When the MAP was only slightly increased (to approximately 130 mm Hg), a trend to flow decrease under NA infusion was observed. Secondly, we compared the effects of NA on rCBF in animals treated or not treated with clorgyline. This was performed under moderate hypertension (within the 'autoregulated' range of MAP) to avoid any risk of mechanical damage to the BBB. Clorgyline administration alone did not significantly modify rCBF, but the subsequent i.v. infusion of NA induced an increase in rCBF (weighted mean 14%) in all structures investigated. The differences being statistically significant (P less than 0.05) in 5 out of 13 structures by up to 20%. Compared to studies involving disruption of the morphological BBB in which plasma NA elicits a widespread important increase in blood flow, the weak cerebrovascular effects we observed provide indirect evidence for the efficiency of the BBB to catecholamines in the conscious rat within the autoregulated range of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Dynamic cerebral and systemic circulatory effects of adenosine, theophylline and dipyridamole.

The effects of intravenous adenosine, dipyridamole and theophylline on local cerebral blood flow were studied in conscious rabbits. Long-term quantitative blood flow measurements were performed in 5 cerebral structures together with tissue pO2 and pCO2 measurements by a mass spectrometry technique. In an additional study, the time course of the cerebrovascular changes was determined by thermal clearance. It was found that: firstly, adenosine failed to modify local blood flow except in the caudate nucleus; secondly, dipyridamole increased cerebral blood flow in all 5 structures under study, and lastly, theophylline decreased cerebral blood flow in the same 5 structures. The increase in caudate blood flow induced by adenosine was instantaneous and lasted only for the duration of the infusion, whereas the cerebrovascular changes induced by dipyridamole and theophylline were gradual and persisted after their administration. Theophylline blocked the systemic and cerebrovascular changes caused by adenosine alone and by dipyridamole alone. In anesthetized rabbits, the intracarotid infusion of adenosine showed that the caudate reaction only occurred in the ipsilateral hemisphere. Taken together, our findings suggest that the transport system for adenosine in cerebral vessels is not only species-dependent but also structure-dependent. Furthermore, perivascular adenosine helps to maintain resting cerebrovascular tone and finally, cerebral adenosine may be involved in the control of cerebral blood flow via specific adenosine receptors.

Adenosine↗

PubMed1988

In vivo 31P nuclear magnetic resonance (NMR) study of cerebral metabolism during histotoxic hypoxia in mice.

The alterations of cerebral energetic metabolism and intracellular brain pH that occur during histotoxic hypoxia were estimated in mice by in vivo 31P nuclear magnetic resonance (NMR) spectrometry. The brain spectra obtained by means of chronically implanted surface coils connected to a special designed probe were recorded sequentially and continuously before, during, and after histotoxic hypoxia induced by an injection of potassium cyanide. The levels of PCr, ATP, inorganic phosphate, and intracellular pH estimated from the records of the 31P cerebral spectra and the cerebral cortical activity allow noninvasive monitoring of both the energetic metabolism and the functional state of the brain in unanesthetized animals. The time courses of these different parameters are largely the same as those obtained previously by invasive methods, however, the simultaneous and continuous monitoring performed in this study exhibits several unexpected dissociations between, respectively, onset of coma, decrease in PCr level and intracellular pHi, and recovery of normal levels of PCr and intracellular pH. These dissociations indicate that tissue acidosis plays a minor role in the changes in PCr levels, compared with ATP, and they confirm that the thresholds of oxidative metabolism required for functional tissue activity and a normal rate of ATP are clearly different.

Animals↗

PubMed1988

Effect of stimulation of the sphenopalatine ganglion on cortical blood flow in the rat.

The effects of electrical stimulation of the sphenopalatine ganglion on cortical blood flow and gas partial pressures (PO2 and PCO2) were studied in the anesthetized rat. Tissue PO2, PCO2, and local CBF were measured simultaneously in both parietal cortices by means of mass spectrometry. Stimulation of the sphenopalatine ganglion increased CBF and tissue PO2 by approximately 50 and 20%, respectively, in the ipsilateral parietal cortex. Smaller but significant increases in CBF and tissue PO2 were simultaneously seen in the contralateral parietal cortex. These variations were also accompanied by small decreases in PCO2 in both parietal cortices and a 5% increase in mean arterial pressure, whereas cortical electrical activity did not change. We conclude that the cholinergic (and vasoactive intestinal polypeptidergic) innervation of the cerebral blood vessels, arising from the sphenopalatine ganglion has significant vasomotor potential and that this system may be of functional importance.

Acetylcholine↗

PubMed1988

Ultrastructural changes in the cerebral artery wall induced by long-term sympathetic denervation.

This study was performed to determine to what extent the morphology of the rabbit middle cerebral artery is affected by the absence of the sympathetic nervous system. Six weeks after unilateral ablation of the superior cervical ganglion, which induced ipsilateral degeneration and disappearance of the perivascular noradrenergic nerve fibers, comparison between the ipsi- and the contralateral middle cerebral arteries revealed that the denervated arterial wall underwent significant thickening. This thickening was principally due to hypertrophy of the smooth muscle cells (SMC), together with an increase in the amount of medial and adventitial collagen. The hypertrophied SMC showed important morphological and ultrastructural modifications--irregular shape, increase in the number of organelles (particularly of Golgi apparatus, free ribosomes, rough endoplasmic reticulum and microtubules), large indented nuclei rich in euchromatin--indicating profound changes in their metabolic and contractile activity which could result in an alteration of their mechanical properties. As these alterations were strictly ipsilateral to the sympathectomy it is likely that they are the direct consequence of the suppression of a regulatory 'trophic' factor linked to the presence of sympathetic nerve fibers. This concept is reinforced by the fact that the first SMC affected are those situated at the media/adventitial border, in the vicinity of adventitial nerve bundles. Thus, the sympathetic nervous system appears to play a key role in the long-term regulation of the cerebral vascular tree structure.

Animals↗

PubMed1987

Metabolism-independent cerebral vasodilation elicited by electrical stimulation of the centromedian-parafascicular complex in rat.

Changes in local cerebral blood flow (1CBF) and local cerebral glucose utilization (1CGU) during electrical stimulation of the centromedian-parafascicular complex in rat have been determined using the autoradiographic [14C]iodoantipyrine and 2-deoxy-[14C]glucose methods. In 40 out of 47 cerebral regions measured, the centromedian-parafascicular complex (CM-Pf) stimulation elicited an increase in 1CBF. The increase in 1CBF was not associated with a rise in cerebral metabolism in 38 regions. Thus, it appears that the activation of CM-Pf neurons or fibers passing through it could play an important role in regulating primary cerebral vasodilation.

Animals↗