Dual innervation of the cerebral arteries

There has been considerable controversy concerning the motor innervation of cerebral arteries. Bayliss et aL (1) and Hill and MacLeod (2) reported no evidence of any vascular response suggesting the existence of vasomotor nerves supplying the vessels of the brain. Dumke and Schmidt (3) also found
little effect of sympathetic stimulation on cerebral blood flow, as did Carlyle and Grayson (4), who concluded that non-nervous autoregulation is the most important factor in the control of cerebral blood flow. The view of these authors (1-4) and others that vasomotor nerves are of minor importance in the
regulation of cerebral blood flow has been supported in recent reviews (5-7), but these conclusions have been recently challenged by James et al. (8), who implicated vasomotor nerves in the responses of cerebral vessels to changes in blood CO2 levels. Earlier than this, Hiirthle (9) and Forbes and Cobb (10) had observed clear responses of cerebral arteries to motor nerve stimulation. Forbes and Cobb observed a constriction of cerebral arteries in response to sympathetic stimulation and a
dilatation, which was blocked by atropine, in response to parasympathetic stimulation.
Meyer et al (11), using a preparation similar to that of Dumke and Schmidt (3), recently
observed a 22 to 30% reduction in internal carotid blood flow when the cervical sympathetic nerve was stimulated.

This work has clearly shown a dual
adrenergic and nonadrenergic innervation of
the anterior cerebral arteries of the rat. Two
types of nerve fiber can be distinguished by
their vesicle inclusions in tissue fixed in
permanganate or, after treatment with 6-
OHDA, in osmium or glutaraldehyde. The
first type contained many small granular
vesicles and degenerated after cervical sympa-
thectomy. Fluorescent, noradrenaline-contain-
ing fibers were detected around the cerebral
arteries; after sympathectomy, these fibers also
degenerated. This suggests that the axons
containing small granular vesicles are adrener-
gic.

Copyright © 1970 American Heart Association. All rights reserved. Print ISSN: 0009-7330. Online ISSN:
TX 72514
Circulation Research is published by the American Heart Association. 7272 Greenville Avenue, Dallas, 1970;26;635-646
Circ. Res.T. IWAYAMA, J. B. FURNESS and G. BURNSTOCK
From the Department of Zoology, University of
Melbourne, Parkville 3052, Victoria, Australia.

This investigation was supported by grants from the
National Heart Foundation of Australia and the
Australian Research Grants Committee.
Dr. Iwayama's permanent address is Department of
Anatomy, Faculty of Medicine, Kyushu University,
Fukuoka, Japan.
Received January 5, 1970. Accepted for publication
March 9, 1970.

Catecholamine influences and sympathetic neural modulation of immune responsiveness

K S Madden, V M Sanders, D L Felten
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
Primary and secondary lymphoid organs are innervated extensively by noradrenergic sympathetic nerve fibers. Lymphocytes, macrophages, and other cells of the immune system bear functional adrenoreceptors. Norepinephrine fulfills criteria for neurotransmission with cells of the immune system as targets. In vitro, adrenergic agonists can modulate all aspects of an immune response (initiative, proliferative, and effector phases), altering such functions as cytokine production, lymphocyte proliferation, and antibody secretion. In vivo, chemical sympathectomy suppresses cell-mediated (T helper-1) responses, and may enhance antibody (T helper-2) responses. Noradrenergic innervation of spleen and lymph nodes is diminished progressively during aging, a time when cell-mediated immune function also is suppressed. In animal models of autoimmune disease, sympathetic innervation is reduced prior to onset of disease symptoms, and chemical sympathectomy can exacerbate disease severity. These findings illustrate the importance of the sympathetic nervous system in modulating immune function under normal and disease states.

the third ventricular floor of the rat following cervical sympathectomy

Various investigators have shown that unilateral ganglionectomy or transection
of the internal and external carotid nerves leads to a regenerative response in
the ipsilateral superior cervical ganglion and to uninjured mature sympathetic
neurons sprouting into bilaterally innervated shared target organs. In this study
changes in the supraependymal neuronal network following unilateral and bi-
lateral cervical sympathectomy on the infundibular floor of the third ventricle
were studied by scanning electron microscopy in comparison with normal and
sham-operated control animals. After unilateral cervical sympathectomy there
was a great increase in the number of varicose nerve fibres on the infundibular
floor as compared to the normal and sham-operated control animals. Not only
was there an increase in the number of nerve fibres, but also their varicosities
were substantially larger than those normally present on the ependymal surface.
This study indicates the possible sympathetic projections from the superior cer-
vical ganglia to the ependymal surface of the third cerebral ventricle.

Folia Morphol.
Vol. 66, No. 2, pp. 94–99
Copyright © 2007 Via Medica
ISSN 0015–5659
www.fm.viamedica.

Adrenergic sympathectomy ablates unmyelinated fibers in the rat 'preganglionic' cervical sympathetic trunk

Classical anatomical depictions of the cervical sympathetic trunk label it as a cholinergic preganglionic structure. We studied the cervical sympathetic trunk of the rat following daily injection for 5 weeks of guanethidine monosulphate, a regimen known to selectively destroy adrenergic neurons outside of the blood-brain barrier leaving cholinergic systems and preganglionic structures intact. The drug-treated animals were compared with a group of physiologic saline-injected animals. In the drug-treated animals, there was an approximately 40% reduction in the numbers of unmyelinated fibers per unit area compared to controls. The finding of swollen and degenerative appearing unmyelinated fibers at 7 days of drug treatment confirmed that the fiber loss resulted from active axonal degeneration. The pattern of unmyelinated fiber loss was expressed as a reduction of fibers per Schwann cell-basement membrane profile with an appearance of 'empty profiles', and a conversion of large profiles (with large numbers of fibers per profile) to smaller size categories. There were no differences in axon diameters, fascicular areas, and numbers of microvessels between the groups. Microvessels were dilated in the drug-treated animals. These findings suggest that a large component of the cervical sympathetic chain in the rat consists of postganglionic adrenergic fibers which appear to intermingle with preganglionic cholinergic axons coursing through the chain.
Brain Res. 1989 Oct 2;498(2):221-8.

http://www.ncbi.nlm.nih.gov/pubmed/2790480?dopt=Abstract

Parasympathetic varicosity proliferation after sympathectomy

Parasympathetic innervation to eyelid smooth muscle inhibits sympathetic neurotransmission pre-junctionally without appreciable direct post-junctional effects. However, 5 weeks after sympathectomy, parasympathetic stimulation elicits substantial cholinergically mediated contractions. This study examined ultrastructural changes accompanying the conversion to parasympathetic excitation. In intact muscles, 64±9 nerve varicosities were encountered per 104 μm2. Most were close to muscle cells and not fully enclosed by supporting cells. Axo–axonal synapses were observed occasionally. Two days following sympathectomy, varicosity numbers were reduced by 97% and, relative to controls, remaining varicosities were farther from muscle cells and more frequently fully enclosed by supporting cells, but contained greater numbers of small spherical and large dense vesicles. By 6 weeks post-sympathectomy, numbers of varicosities per unit muscle volume increased to 14% of controls. These varicosities differed from those at 2 days in being closer to smooth muscle cells, less frequently enclosed, and having fewer small vesicles. These findings indicate that intact eyelid smooth muscle varicosities are predominantly sympathetic, but a small number of parasympathetic varicosities are present, some of which may form pre-junctional synapses with sympathetic nerves. Between 2 days and 6 weeks post-sympathectomy, varicosities increased in number and established appositions with smooth muscle cells. This suggests that parasympathetic nerves are capable of re-innervating an atypical smooth muscle target after sympathectomy, and that parasympathetic synaptogenesis is likely to contribute to conversion from pre-junctional inhibition to post-junctional excitation after sympathectomy.
Brain Research
Volume 786, Issues 1-2, 9 March 1998, Pages 171-180

Ultrastructural changes in the nerves innervating the cerebral artery after sympathectomy

The ultrastructure of the innervation of the anterior cerebral artery of the rat was studied in control animals and in animals after superior cervical ganglionectomy.
Fluorescence histochemistry shows a periarterial network of intensely fluorescent fibers which are divided into two groups, adventitial and periadventitial. The fluorescence begins to decrease 26 hours after, and completely disappears about 32 hours after, ganglionectomy.
Fine structural changes are first observed 18 hours after ganglionectomy, when the axoplasm of degenerating axons becomes electron dense. This density gradually increases up to about 32 hours. By 32 hours most axons with disintegrating axolemmas become inclusion bodies of the Schwann cells. At this stage, synaptic vesicles can still be distinguished as less dense areas, but the membrane structures of synaptic vesicles and mitochondria are difficult to recognize. The degenerating axons are gradually absorbed and by 38 hours dense, residual bodies are observed in the Schwann cells. Generally speaking, the degeneration occurs first in the adventitial fibers and then in the periadventitial fibers. The transient appearance of small, granular vesicles is noticed in axon terminals about 18 hours after denervation, although very few small, granular vesicles are seen in control tissue or at later stages of degeneration.
Cell and Tissue Research
Publisher Springer Berlin / Heidelberg
ISSN 0302-766X (Print) 1432-0878 (Online)
Issue Volume 109, Number 4 / December, 1970