Dual adrenergic and cholinergic innervation of the cerebral arteries of the rat. An ultrastructural study.
TL;DR: The innervation of the anterior cerebral artery of the rat was examined by electron microscopy and by the fluorescence method for localizing adrenergic nerves and both adrenergic and cholinergic axons come into close relationship with smooth muscle cells.
Abstract: The innervation of the anterior cerebral artery of the rat was examined by electron microscopy and by the fluorescence method for localizing adrenergic nerves. Two groups of axon bundles were associated with the artery; one at the outer margin of the adventitia ( periadventitial bundles) and the other within the adventitia or at the adventitia-media border ( adventitial bundles). Periadventitial bundles consisted of nonmyelinated axons (0.1-2µ diam), some of which contained synaptic vesicles; in some bundles, myelinated axons were seen. Adventitial axons often contained many synaptic vesicles and were free of Schwann cell sheath in areas apposed to smooth muscle cells. The closest observed approach of axon to muscle cell was 800 A. No nerve fibers penetrated the medial muscle. After fixation with glutaraldehyde plus osmium, large (1000 A) granular and small (500 A) agranular vesicles were seen within many axon profiles. Small granular vesicles were rare. After permanganate fixation, terminal axons contained (besides large granular vesicles) either predominantly small granular vesicles or exclusively small agranular vesicles. Two days after sympathetic denervation, no axons containing small granular vesicles and no fluorescent fibers were seen. Adrenergic fibers were readily identified after injection of rats with 6-hydroxydopamine; small vesicles of adrenergic axons contained highly opaque granular cores, even in osmium-fixed material. Axons containing small agranular vesicles after 6-hydroxydopamine were considered cholinergic. The density of granulation of the large vesicles of adrenergic, but not cholinergic, axons was considerably enhanced following 6-hydroxydopamine. Both adrenergic and cholinergic axons come into close relationship with smooth muscle cells.
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TL;DR: The published PET data describe a very reproducible functional neuroanatomy in sleep, and more detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques, which will contribute to a better understanding of sleep functions.
Abstract: Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this 'canonical' sleep may be summarized as follows. In slow-wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid-eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.
630 citations
Cites background from "Dual adrenergic and cholinergic inn..."
...The most intriguing ®nding suggesting neurogenic control of local CBF is the presence of nerve ®bres in the vicinity of cerebral vessels (Iwayama et al. 1970; Edvinsson et al. 1972)....
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01 Jan 2000
516 citations
TL;DR: The amine mechanisms demonstrated in human brain vessels appear to be principally the same of those shown in more extensive studies on laboratory animals.
431 citations
TL;DR: In the present study cerebral blood flow was measured simultaneously in multiple small areas of the brain of nonanesthetized man during direct intracarotid infusion of the drugs.
Abstract: In recent years there has been renewed ininterest in the possible role of the autonomic nervous system in the regulation of cerebral blood flow. Histochemical techniques have clearly shown the abundant network of autonomic nerves around the basal and pial arteries of the brain.' Electron-microscopic studies have confirmed that these nerves terminate in contact with the vascular smooth muscles in the same way as in other organs where the physiologic importance of the autonomic nerves is well est a b l i ~ h e d . ' ~ L o c a l appl ica t ion of catecholamines has been shown t o constrict the basal and pial cerebral and this response can be blocked pharmac~logica l ly .~ >7 Despite these achievements the effect of circulating catecholamines is not yet clear, as will be reviewed below in the Discussion. Circulating catecholamines might well play a n important role in the pathogenesis of cerebral vasospasm as seen in subarachnoid hemorrhage and presumably also in the initial phase of a migraine attack. The drugs still are used in the treatment of shock and the regulation of blood pressure during anesthesia. In these situations a cerebral vasoconstrictor effect would be highly disadvantageous. On this basis it was considered pertinent to derive data of clinical relevance regarding the effects of circulating catecholamines on the cerebral blood flow. In the present study cerebral blood flow was measured simultaneously in multiple small areas of the brain of nonanesthetized man during direct intracarotid infusion of the drugs.
259 citations
TL;DR: The origin and distribution of sympathetic and sensory innervation to major cerebral arteries in the rat is demonstrated and anterograde labelling of nerve fibres on whole-mounts of the cerebral vessels is demonstrated.
189 citations
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TL;DR: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenientembedding methods for electron microscopy.
Abstract: Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenient embedding methods for electron microscopy. The sections are robust and tissue damage is less than with methacrylate embedding.
9,741 citations
TL;DR: In the present study great emphasis will be put on information regarding cerebral oxygen consumption in man, whereas only scant attention will be paid to the intermediary metabolism of the brain.
Abstract: HE BLOOD FLOW AND OXYGEN METABOLISM of the human brain has been studied intensively since Kety developed the inert gas method in 1945. More than 200 clinical studies employing this method have been published so far, and now the former terra incognita is well mapped out. The information gained from all these studies will form the subject of the present review. It will also include, however, the results obtained by an indicator injection technique which has been applied to the measurement of cerebral blood flow in man to a much more limited extent. The early results obtained in this particular field have been reviewed by Schmidt (292) and Kety (156-163) and by other authors (38, 61, 76, 2 I 6, 281, 307). The aim of the present review is to offer an up to date presentation of the subject, and, in particular, to discuss certain aspects in greater detail. The general field of cerebral circulation was reviewed by Wolff in 1936 (348), by many authors in a comprehensive study in 1938 (41), and extensive bibliographic compilations of original contributions from 1938 to 1952 have also been published (255, 256). The pharmacology of the cerebral circulation alone, which has recently been reviewed by Sokoloff (318), forms an overwhelming body of knowledge. In the present study great emphasis will be put on information regarding cerebral oxygen consumption in man, whereas only scant attention will be paid to the intermediary metabolism of the brain. Himwich in I 951 published an excellent review (142) of much of the pertinent literature in this rapidly expanding field. Reference is also made to the recent study by Sokoloff (3 I 9). The first attempt to measure the cerebral blood flow in man was made in 1941 by observing the displacement of spinal fluid caused by compression of the
1,852 citations
TL;DR: Among several heavy metal salts tested, the above-ment ioned " lead hydroxide" of Watson seemed to be the most effective in "s ta in ing ." Exper iments with the commercial ly available product showed that this salt would give no impregna t ion when dissolved in water, or in Institute.
Abstract: Meta l impregnat ion , or "s ta in ing ," of tissue sections for electron microscopy has become the accepted practice in recent years. Salts of metals of h igh atomic weight such as u ran ium, chromium, thor ium, lead, or tungsten, among many tested, have been found suitable (6, 1). "Lead hydroxide ," as prepar ted by Watson (6), is now widely used, hu t this solution is extremely unstable in air and becomes covered by a meta l l ic-appear ing film which imparts to the " s ta ined" section a well known deposit of e lectron-opaque particles and crystals, reducing considerably the percentage of clean areas suitable for micrography (Fig. l) . Several procedures and devices have been described to lessen these contaminat ions. Peachey (5), using lead hydroxide, or subacetate, found tha t if the solution is kept in a syringe with the protect ing cap filled with sodium hydroxide to absorb the CO2 of the atmosphere, con tamina t ion is reduced. More recently, a fairly unwieldy appara tus has been suggested for the same purpose (4). Tests performed in our laboratory in which " s t a in ing" was a t tempted in a chamber under cont inuous ni t rogen flow and in the presence of a ba r ium chloride t rap were not completely successful, which is to say tha t con tamina t ion cont inued to be a problem. A n u m b e r of o ther var iat ions have been recommended. Lever (2), e.g., described a method for prepar ing a " s t a in ing" solution by adding potassium hydroxide to a lead hydroxide solution. To dissolve some of the occasionally formed crystals of contamina t ion , the sections are rinsed afterwards for a few seconds in a weak potassium hydroxide solution; this step is very critical because the "s ta in ing" is also weakened by the alkali and uni form staining is difficult to achieve. These various shortcomings of current ly avai lable methods have st imulated us to search for a lead salt tha t would not be affected by the components of the atmosphere. Among several heavy metal salts tested, the above-ment ioned " lead hydroxide" of Watson seemed to be the most effective in "s ta in ing ." Exper iments with the commercial ly available product showed that this salt would give no impregna t ion when dissolved in water, or in Institute. Dr. Millonig's present address is Biological
1,310 citations
TL;DR: Wurden Katzen mit 2×14 und 2×34 mg/kg 6-OH-DA intravenös behandelt, so betrug eine Woche nach Verabreichung der letzten Dosis der Noradrenalingehalt im Herzen 7,6%, in der Milz 5,1% and im Vas deferens 18,8% des Gehaltes entsprechender Kontrollen.
Abstract: After electronmicroscope studies had shown that 6-hydroxydopamine (6-OH-DA) induced a selective destruction of adrenergic nerve terminals, we studied the correlation between the dose-dependent norepinephrine depletion by 6-OH-DA and its uptake and storage in sympathetically innervated organs. We also investigated whether 6-OH-DA can be used for general chemical sympathectomy.
808 citations
TL;DR: Following intravenous infusion of tritiated norepinephrine, rat pineals were prepared for combined autoradiography and electron microscopy and Concentrations of photographic grains were observed only over regions of preterminal autonomic axons containing granulated vesicles, thereby directly demonstrating uptake of norpinephrine into these axons and strongly suggesting that their granulatedVesicles contain nore Pinephrine.
Abstract: Following intravenous infusion of tritiated norepinephrine, rat pineals were prepared for combined autoradiography and electron microscopy. Concentrations of photographic grains were observed only over regions of preterminal autonomic axons containing granulated vesicles, thereby directly demonstrating uptake of norepinephrine into these axons and strongly suggesting that their granulated vesicles contain norepinephrine.
414 citations