Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

Iadecola, Costantino; Nakai, Masatsugu; Mraovitch, Sima; Ruggiero, David A.; Tucker, Lewis W.; Reis, Donald J.

doi:10.1016/0006-8993(83)90367-0

Cited by 74 publications

(33 citation statements)

References 34 publications

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“…It is also unlikely that these drugs act on cerebral metabolism because NOS inhibition does not affect resting cerebral glucose utilization (9) or the cerebrovasodilation elicited by stimulation of the pontine reticular formation, which is highly sensitive to agents that decrease cerebral metabolism (17,43). The stereospecificity of the reversal of the NA block by L-Arg but not D-Arg strongly suggests competition for a specific binding site (presumably the active site of NOS) rather than a nonspecific vasodilatory effect.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Vasconcelos¹,

Baldwin²,

Wasterlain³

1995

Proc. Natl. Acad. Sci. U.S.A.

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The role of nitric oxide (NO) in the increase in local cerebral blood flow (LCBF) elicited by focal cortical epileptic seizures was investigated in anesthetized adult rats. Seizures were induced by topical bicuculline methiodide applied through two cranial windows drilled over homotopic sites of the frontal cortex, and LCBF was measured by quantitative autoradiography by using 4-iodo[N-methyl-14C]antipyrine. Superfusion of an inhibitor of NO synthase, N1"-nitro-L-arginine (NA; 1 mM), for 45 min abolished the increase of LCBF induced by topical bicuculline methiodide (10 mM) [164 ± 18 ml/100 g per min in the artificial cerebrospinal fluid (aCSF)-superfused side and 104 + 12 ml/100 g per ml in the NA-superfused side; P < 0.005]. This effect was reversed by coapplication of an excess of L-arginine substrate (10 mM) (218 ±-22 ml/100 g per min in the aCSF-superfused side and 183 ± 31 ml/100 g per min in the NA + L-Arg-superfused side) but not by 10 mM D-arginine, a stereoisomer with poor affinity for NO synthase (193 ± 17 ml/100 g per min in the aCSF-superfused side and 139 ± 21 ml/100 g per min in the NA + D-Arg-superfused side; P < 0.005). Superfusion of the guanylyl cyclase inhibitor methylene blue attenuated the LCBF increase elicited by topical bicuculline methiodide by 25% ± 16% (P < 0.05). The present findings suggest that NO is the mediator of the vasodilation in response to focal epileptic seizures.Nitric oxide (NO) or a closely related NO-containing compound that is synthesized from L-arginine has been identified as one of the endothelium-derived relaxing factors which modulate vascular responses to various stimuli by activation of soluble guanylyl cyclase (1-3). NO plays an important role in the regulation of the basal cerebral circulation (4-9) and modulates cerebral blood flow during hypercapnia (7,8,10, 11), local neuronal activation (12-16), or activation of intracerebral neural pathways (17, 18). However, NO may not be involved in cerebrovascular responses to stimulation of reticular formation (17), to somatosensory stimulation (19), and to some hypoxic stimuli (5,8, 11). NO has also been suggested to be an important transmitter in the. central nervous system (20-23) and may represent a major mechanism to couple local perfusion with neuronal activity (14,15,24).The mechanisms regulating increases in cerebral blood flow in response to seizures have not been clearly defined, although different substances like HI, C02, K+, prostaglandins, and adenosine might be involved (25)(26)(27).The present experiments were performed to study the role of NO in cerebral vasodilation during focal seizure activity in anesthetized adult rats. NO is synthesized from L-arginine by NO synthase (NOS) (28,29). NOS activity can be inhibited by No-substituted arginine such as Nw-nitro-L-arginine (NA) (3, 30). Furthermore, NO exerts its vasodilating action by acti-The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accorda...

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Section: Discussionmentioning

confidence: 99%

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Vasconcelos¹,

Baldwin²,

Wasterlain³

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…Key Words: Autoradiogra phy-Direct current potential-Electrocorticogram Focal ischemia-Image analysis-Local cerebral blood flow-Local cerebral glucose utilization. deoxy-o-glucose (2-DG) (Sokoloff et aI., 1977), it was demonstrated that tight regional coupling of glucose metabolism and blood flow existed in vari ous brain structures under normal conditions (Rei vich, 1974;Ginsberg et aI., 1986) and in a variety of states including functional activation (Sokoloff, 1981; Ginsberg et aI., 1987), electrical brain stimu lation (Iadecola et al, 1983), and metabolic acidosis (Kuschinsky et aI., 1981).…”

mentioning

confidence: 99%

Three-Dimensional Image Analysis of Brain Glucose Metabolism-Blood Flow Uncoupling and its Electrophysiological Correlates in the Acute Ischemic Penumbra following Middle Cerebral Artery Occlusion

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Zhao

Ginsberg

1995

J Cereb Blood Flow Metab

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Summary:The relationship between local cerebral glu cose utilization (LCMRglc) and local CBF (LCBF) is known to be disturbed in regions surrounding an acute focal ischemic lesion-areas that undergo repeated tran sient depolarizations. In this study, we evaluated the re lationship between LCMRglc and LCBF in the acute focal ischemic penumbra to quantify metabolism-flow uncou pling, and we related these findings to local electrophys iological measurements. A novel strategy utilizing three dimensional (3D) autoradiographic image averaging yielded group 3D reconstructions of LCBF, LCMRg 1C' and the CMRlCBF ratio. The distal right middle cerebral artery of Sprague-Dawley rats was occluded by laser driven photothrombosis following administration of the photosensitizing dye rose bengal; this was coupled with permanent ipsilateral and I-h contralateral common ca rotid artery occlusions. LCBF (n = 7) and LCMRglc (n = 7) were measured autoradiographically at 1.25 and 1.5-2 h postocclusion, respectively, in matched animal groups. Within the ischemic penumbra (defined as having LCBF of 20-40% of control or 0.23-0.47 ml g-J min -J ) , LCM Rglc showed a heterogeneous pattern with values ranging Coupling of cerebral metabolism and blood sup ply was first described by Roy and Sherrington 566from near normal to markedly increased. The resulting CMRglc/CBF ratio in this zone was 234 ± 100 fl-moUlOO ml (mean ± SD), representing a severe degree of metab olism-flow dissociation when compared with the CMRglcl CBF ratio of 51.0 ± 28.7 fl-molll00 ml of the contralateral (normal) hemisphere. Metabolism-flow uncoupling was confined to the ipsilateral cortex and was most prominent at the anterior and posterior coronal poles of the ischemic lesion. In the frontoparietal penumbra, where marked un coupling was observed, sustained deflections of the DC potential were recorded, which increased significantly in duration over the initial 65 min postocclusion. Both the heterogeneous pattern of LCMR Ie and the widespread distribution of increased CMRgJCBF ratio in the isch emic penumbra are thought to reflect the metabolic con sequences of periinfarct depolarizations. Analysis of av eraged 3D autoradiographic data sets provides a powerful means for assessing metabolism-flow uncoupling sur rounding an ischemic focus.

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“…Increases in glucose metabolism during activation are the basis of the classical functional mapping techniques, 2-deoxyglucose autoradiography (see Sokoloff [2] for review) and positron emission tomography (PET) (see Phelps et al [3] for review). Glucose metabolism, in turn, is coupled to cerebral blood flow under normal conditions [4][5][6]. The combined effects of glucose metabolism and blood flow on local hemoglobin oxygenation provide image contrast for the Sibson/Shen/Mason/Rothman/Behar/ Shulman more recently developed functional magnetic resonance imaging (FMRI) method of mapping brain activity (see DeYoe et al [7] for review).…”

Section: Introductionmentioning

confidence: 99%

Functional Energy Metabolism:In vivo <sup>13</sup>C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity

Sibson¹,

Shen²,

Mason³

et al. 1998

Dev Neurosci

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The use of in vivo ¹³C nuclear magnetic resonance spectroscopy (NMR) has established the pathways of functional interaction between neurons and astrocytes in the mammalian brain and enabled quantitation of these fluxes. A mathematical model of glutamate, glutamine and ammonia metabolism in the brain has been developed, under the constraints of carbon and nitrogen mass balance, allowing the direct and quantitative comparison of in vivo ¹³C- and ¹⁵N-NMR data. Using this model and ¹³C-NMR data, the authors have separated the neurotransmitter cycling and detoxification components of glutamine synthesis by measuring the rate of glutamine synthesis under normal and hyperammonaemic conditions in the rat brain cortex in vivo. In addition, the simultaneous measurement of the rates of oxidative glucose metabolism and glutamate neurotransmitter cycling in the rat brain cortex has shown that over a range of EEG activity (from isoelectric up to near-resting levels) the stoichiometry between glucose metabolism and glutamate cycling is close to 1:1. Under mild anesthesia, cortical glucose oxidation coupled to glutamatergic synaptic activity accounts for over 80% of total glucose oxidation. Previously, changes in cerebral glucose metabolism have been taken to indicate alterations in functional activity. These recent in vivo results demonstrate, however, that those changes are, in fact, quantitatively coupled to the crux of functional activity, neurotransmitter release. These findings bear upon a number of hypotheses concerning the neurophysiological basis of brain functional imaging methods.

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Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

Cited by 74 publications

References 34 publications

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Three-Dimensional Image Analysis of Brain Glucose Metabolism-Blood Flow Uncoupling and its Electrophysiological Correlates in the Acute Ischemic Penumbra following Middle Cerebral Artery Occlusion

Functional Energy Metabolism:In vivo <sup>13</sup>C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity

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