The anatomy and phylogenetic significance of the carotid arteries and nerves in strepsirhine primates

The internal carotid artery in lorisiform primates was identified on the basis of its close association with the internal carotid nerve (postsynaptic sympathetic trunk). An atrophic vessel in the lorisine Arctocebus resembles the internal carotid artery of Lemur in that it enters the tympanic bulla and promontory tube closely associated with the internal carotid nerve. According to this criterion of homology, the enigmatic lorisiform extrabullar carotid artery is not homologous with the internal carotid (promontory) artery of lemuriform primates or the medial internal carotid artery of the dog. Hypotheses about strepsirhine evolution must take these morphological facts into account.     

The homologies of the lorisoid internal carotid artery system

The development of the “internal carotid” arterial system of the lesser galago (Galago senegalensis senegalensis)is described. The first artery to be formed is a typical promontory artery which runs through the middle-ear cavity and gives off the stapedial artery. It terminates in the cranial cavity by dividing into the middle cerebral, anterior cerebral, and two ophthalmic arteries. It is accompanied by the internal carotid nerve. A medially directed artery to the external carotid rete arises from the commencement of the promontory artery and joins the caudal end of the rete, whose cranial end lies in the foramen lacerum. As the promontory artery enters the cranial cavity, it communicates with the cranial end of the rete. The promontory artery, between the origin of the artery to the rete and its connection with the rete, becomes narrowed and eventually disappears. Thus the internal carotid artery is formed from the commencement of the promontory artery, the artery to the rete, the external carotid rete, and the terminal intracranial part of the promontory artery. The relationships of the artery to the rete indicate that it is the homologue of the human ascending pharyngeal artery.     

The primitive course of the internal carotid artery in mammals.

In all recent mammals the internal carotid artery at the level of the auditory capsule is derived from the embryonic dorsal aorta. In adults of various groups, the artery lies in positions which are classified as medial or promontory. It is shown that these character states arise by a process of differential growth affecting the relative positions of the dorsal aorta and the cochlear promontory. There is no evidence for separate vessels in the embryo which could give rise to non-homologous internal carotid arteries in the two positions. It follows that the concept of a primitive mammalian morphotype with both a medial and a promontory internal carotid artery in the same individual presents a formidable embryological problem. It is recommended that, in the absence of supporting evidence, the widespread current taxonomic and palaeontological use of this hypothetical morphotype should be regarded with suspicion.     

Vasoactive-intestinal-polypeptide (VIP)-like immunoreactive cells in the skull base of rats. A combined study using acetylcholinesterase histochemistry

We investigated the distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies in relation to the major cerebral and internal carotid arteries at the skull base in rats. Acetylcholinesterase (AChE) histochemistry was also applied to investigate the localization of this enzyme. VIP staining revealed a few positive cell bodies in nerves close to the internal carotid artery at the base of the skull as well as in the cerebral arterial wall. Ganglion-like cell bodies were detectable within the greater superficial petrosal (GSP) nerve. AChE activity was observed in VIP-like immunoreactive cell bodies along the whole of the GSP nerve. These cell bodies in the GSP nerve may give rise to at least some of the perivascular VIP- and AChE-containing nerves of the internal carotid arteries at the base of the skull.     

The petrosal of Omomys carteri and the evolution of the primate basicranium

The first omomyine petrosals, those of Omomys carteri, are described. Omomys probably had a tympanic bulla and canals for the intratympanic carotid circulation derived from the petrosal bone. The stapedial and promontory canals were complete, large and subequal. The posterior carotid foramen entered the bulla posteromedially. The intratympanic portion of the facial nerve was fully enclosed in bone, the stapedius fossa is extrabullar and the parotic fissure is patent. The mastoid was pneumatized from the epitympanic recess and a supracochlear cavity may have been present. The Omomys petrosals exhibit a generic omomyiform morphology, exhibiting no features that can be interpreted as autapomorphies and only one feature shared with adapiforms. The monophyly of Omomyiformes is based on other cranial characters, dental and postcranial characters assessed elsewhere. The similarity of the Shanghuang petrosal to the petrosals of omomyiforms, as well as the ambiguous evidence of its association, suggest that an omomyiform affinity for that petrosal cannot be ruled out.     

Sympathetic innervation of the carotid bifurcation in the rabbit and cat: Blood vessels,carotid body and carotid sinus

Summary Two postganglionic branches of the superior cervical ganglion enter the area of the carotid bifurcation in the rabbit and the cat. The common and external carotid arteries receive a rich adrenergic nerve supply, which can be demonstrated by fluorophores of biogenic amines appearing after formaldehyde treatment. The internal carotid artery is only sparsely innervated; however, it shows a dense sympathetic supply at the site of pressor receptors. Following removal of the superior cervical ganglion, a total loss of fluorescent adrenergic nerves occurs and degeneration of nerve endings possessing dense core vesicles is conspicuous. These nerve terminals are situated mainly subendothelially in the carotid body sinusoids; they only rarely terminate on type I cells.     

Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern.

The phase-dependent plasticity of carotid chemoafferent signaling was studied with electrical stimulation of a carotid sinus nerve during either inspiration or expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated rats. Stroboscopic and interferometric analyses of the resulting phase-contrast disturbances of the respiratory rhythm revealed that carotid chemoafferent traffic was dynamically filtered centrally by a parallel bank of leaky integrators and differentiators, each being logically gated to the inspiratory or expiratory phase in a stop-and-go manner as follows: 1) carotid short-term potentiation of inspiratory drive was mediated by dual integrators that both shortened inspiration and augmented phrenic motor output cooperatively in long and short timescales; 2) carotid short-term depression of respiratory frequency was mediated by a (possibly pontine) integrator that lengthened expiration with a relatively long memory; and 3) carotid "chemoreflex" shortening of expiration was mediated by an occult fast integrator, which, together with carotid short-term depression, formed a differentiator. These effects were modulated anteriorly by integrators in the nucleus tractus solitarius that were "auto-gated" to, or recruited by, the carotid sinus nerve input. Such phase-selective and activity-dependent time-frequency filtering of carotid chemoafferent feedback in parallel neurological-neurodynamic central pathways may profoundly affect respiratory stability during hypoxia and sleep and could contribute to the dynamic optimization of the respiratory pattern and maintenance of homeostasis in health and in disease states.     

Electron microscopic structure and innervation of the carotid baroreceptor region in the rock hyrax (Procavia capensis).

Semi-thin plastic sections reveal that the carotid baroreceptor region in the rock hyrax comprising the origin of the internal carotid artery has a preponderantly elastic structure and a thick tunica adventitia. In contrast, the common carotid artery has a musculoelastic structure, whereas the cranial segment of the internal carotid artery (immediately distal to the baroreceptor areas) shows the features of a muscular artery. Electron microscopy discloses the presence of sensory nerve endings within the parts of the tunica adventitia adjoining the preponderantly elastic zone of the internal carotid artery. These nerve endings are characterized by varicose regions containing a large quantity of mitochondria. Bundles of collagen fibers in the tunica adventitia form convolutions or whorls around the nerve terminals and often terminate on the surface of the elastic fibers or into the basement membranes of the neuronal profiles. The large content of elastic tissue in the tunica media of the baroreceptor region may render the vessel wall highly distensible to intraluminal pressure changes. This, in turn, would facilitate the transmission of the stimulus intensity to the sensory nerve terminals located in the tunica adventitia. It is suggested that the stretching of elastic fibers may form the main mechanical event leading to the distortion of the associated nerve terminals. However, a change in the geometrical configuration of the bundles of collagen under the influence of the elastic fibers may provide a better insight into the mechanisms of distortion of the baroreceptors related to and/or in contact with collagen fibers.     

Vasoactive-intestinal-polypeptide (VIP)-like immunoreactive cells in the skull base of rats

Summary We investigated the distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies in relation to the major cerebral and internal carotid arteries at the skull base in rats. Acetylcholinesterase (AChE) histochemistry was also applied to investigate the localization of this enzyme. VIP staining revealed a few positive cell bodies in nerves close to the internal carotid artery at the base of the skull as well as in the cerebral arterial wall. Ganglion-like cell bodies were detectable within the greater superficial petrosal (GSP) nerve. AChE activity was observed in VIP-like immunoreactive cell bodies along the whole of the GSP nerve. These cell bodies in the GSP nerve may give rise to at least some of the perivascular VIP-and AChE-containing nerves of the internal carotid arteries at the base of the skull.     

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.     

Evidence for GABAergic fibers entering the superior cervical ganglion of rat from the preganglionic nerve trunk

The origin of gamma-aminobutyric acid immunoreactive (GABA-IR) nerve fibers present in the superior cervical ganglion (SCG) of rat was investigated. With immunocytochemical techniques many nerve fibers showed GABA-like positivity in the cervical sympathetic trunk, whereas similar staining could not be revealed in the internal carotid nerve or in the external carotid nerve. Ligation of the cervical sympathetic trunk for 24 h resulted a dramatic reduction in the staining density in the ganglion and in the cervical sympathetic trunk distal to the ligature. After transection of the preganglionic nerve fibers for eleven days or more, very few fibers staining for GABA were seen in the ganglion. The immunohistochemical results suggest that a major source of GABA within the SCG is a population of GABAergic axons entering from the preganglionic trunk.     

Evidence for GABAergic fibers entering the superior cervical ganglion of rat from the preganglionic nerve trunk

Summary The origin of gamma-aminobutyric acid immunoreactive (GABA-IR) nerve fibers present in the superior cervical ganglion (SCG) of rat was investigated. With immunocytochemical techniques many nerve fibers showed GABA-like positivity in the cervical sympathetic trunk, whereas similar staining could not be revealed in the internal carotid nerve or in the external carotid nerve. Ligation of the cervical sympathetic trunk for 24 h resulted a dramatic reduction in the staining density in the ganglion and in the cervical sympathetic trunk distal to the ligature. After transection of the preganglionic nerve fibers for eleven days or more, very few fibers staining for GABA were seen in the ganglion. The immunohistochemical results suggest that a major source of GABA within the SCG is a population of GABAergic axons entering from the preganglionic trunk.     

The inhibition of efferent sympathetic activity by means of pressure stimulation of the carotid sinus pressoreceptors]

The influence of pressure stimulation of a barorecptor upon the activity of the sympathetic nerve branch terminating in the wall of the contralateral carotid bifurcation was studied on narcotized dogs. The potential activity of this branch is of efferent nature. On the average, 570 msec after the pressure load applied to the opposite carotid sinus preparation, a silent period occurred. The duration of this silent period and the activity of the sympathetic nerve branch depend on the internal pressure of the preparation. The influence of different structures (central and peripheral) on latency, total and partial inhibition of the sympathetic activity are discussed.     

Anatomical variations of the intracavernous branches of the internal carotid artery with reference to the relationship of the internal carotid artery and sixth cranial nerve. A microsurgical study

Thirty cavernous sinuses were dissected and examined using microsurgical methods under a magnification of X10 and X16. The anatomical variations of the intracavernous branches of the internal carotid artery (ICA) and the anatomical relationship of the sixth nerve with the ICA are described and discussed in relation to the findings from other microsurgical works.     

Innervation of the carotid body. An experimental quantitative study

The innervation of the carotid body in the cat was studied by means of light- and electron-microscopic techniques. Sinus nerve resection, glossopharyngeal resection, bilateral cervical sympathectomy, excisions of two nerves, and injection of 6-hydroxydopamine (6-OH-DA) were performed in different groups of animals. It was found that resection of the sinus nerve produces a rapid phase of degeneration of intralobular fibers and synaptic boutons, followed by a reinnervation with a progressive reappearance of these elements. This reinnervation is retarded by sympathectomy and prevented by 6-OH-DA. It is therefore concluded that reinnervation is due to collateral regeneration of nearby sympathetic fibers. Resection of the sinus nerve produces an increase in the number of argentaffin cells and dense-cored vesicles in the cytoplasm of principal cells. These findings suggest the existence of efferent synaptic contacts between this nerve and principal cells. Part of the intralobular fibers and synaptic boutons degenerate after bilateral sympathectomy demonstrating that sympathetic axons connect synaptically to the principal cells. Sympathetic fibers reach the carotid body, not only from branches of the cervical plexuses but also from fibers running in the adventitia of the common carotid artery, and via glossopharyngeal and sinus nerves. The vagus nerve contributes a few fibers to the parenchymal lobules of the carotid body.     

Biphasic ventilatory response of adult cats to sustained hypoxia has central origin

Hypoxia stimulates ventilation, but when it is sustained, a decrease in the response is often seen. The mechanism of this depression or "roll off" is unclear. In this study we attempted to localize the responsible mechanism at one of three possible sites: the carotid bodies, the central nervous system (CNS), or the ventilatory apparatus. The ventilatory response to sustained hypoxia (PETO2, 40-50 Torr) was tested in 5 awake and 14 anesthetized adult cats. The roll off was found in both anesthetized and awake cats. Isocapnic hypoxia initially increased ventilation as well as phrenic and carotid sinus nerve activity in anesthetized cats (288 +/- 31, 269 +/- 31, 273 +/- 29% of control value, respectively). During the roll off, ventilation and phrenic nerve activity decreased similarly (to 230 +/- 26 and 222 +/- 28%, respectively after the roll off), but in contrast carotid sinus nerve activity remained unchanged (270 +/- 26%). Thus the ventilatory roll off was reflected in phrenic but not in carotid sinus nerve activity. We conclude that the cat represents a useful animal model of the roll off phenomenon and that the mechanism responsible for the secondary decrease in ventilation lays within the CNS.     

Adrenergic and cholinergic components of the innervation of the arteries of the base of the bird brain

By means of Falck's and Koelle's methods adrenergic and cholinergic structures were studied in the arteries in the cerebral basis of blue rock pigeons and of hens, white leghorn stock. The number of nerve transmitters was estimated per 1 mm2 of the vessel surface. The arteries of the basis in pigeon brain are surrounded with developed adrenergic and cholinergic nerve plexuses, their density decreasing in the following order: nasal branch of the internal carotid artery, middle, nasal cerebral and basilar arteries. A little more cholinergic transmitters occur on the middle cerebral artery, while on the other vessels, concentration of cholinergic and adrenergic fibers is equal. In hens, the density in the arrangement of adrenergic nerve transmitters is higher in the nasal branch of the internal carotid and in the nasal cerebral arteries than in the basilar artery. At the same time, chromaffin cells forming numerous conglomerations in some places are found on the latter. In pigeons, the density of adrenergic fibers arrangement on the arteries of the cerebral basis is higher than in hens.     

Application of stereotactic principles to the treatment of trigeminal neuralgia.

The application of neuroanatomical and neurophysiological principles to the functional surgery of the trigeminal nerve is discussed. Particular attention has been directed toward correlating the three-dimensional anatomical features of the trigeminal nerve and the surrounding structures to the two-dimensional radiograph of this same region. In this regard, 20 trigeminal nerves, including the surrounding neurovascular structures from 10 cadaver sphenoid blocks, were examined. Measurements of the third, fourth and sixth cranial nerves in relation to the profile of the clivus were made from lateral radiographs of the sphenoid blocks. The position of the internal carotid artery in relation to these structures was also noted. These neurovascular relationships are of clinical importance when using the percutaneous thermocoagulation technique for the treatment of trigeminal neuralgia.     

Ultrastructure of calcitonin gene-related peptide-and substance P-like immunoreactive nerve fibres in the carotid body and carotid sinus of the guinea pig

Summary Previous studies have demonstrated that substance P-(SP) and calcitonin gene-related peptide-like immunoreactivities (CGRP-LI) coexist in sensory nerve fibres in the guinea-pig carotid body and carotid sinus. In the present study the ultrastructure of these nerve fibres was investigated by means of single-and double-labelling immunocytochemistry. In both, carotid body and carotid sinus immunoreactive fibres were unmyelinated axons of small dianeter (0.12–0.56 m). At the subcellular level, SP-and CGRP-LI were colocalized in intra-axonal dense core vesicles, suggesting corelease and simultaneous action of these two compounds. SP/CGRP-LI nerve fibres within the carotid body were mainly found in the interparenchymal connective tissue, but also occurred in relationship to blood vesslesl and nests of glomus cells. Neither in the carotid body not in the carotid sinus, SP/CGRP-LI axons corresponded to the large terminals which are generally considered to represent the main chemoreceptor and baroreceptor endings, respectively. Thus, SP/CGRP-LI fibres either belong to the chemo-and baroreceptors of the C-fibre class or constitute a fibre population not directly involved in conduction of baro-and chemoreflexes.This study was supported by the DFG, grant He 919/6-2     

FRS2 alpha 2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve

The docking protein FRS2α is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. We show that the carotid body is absent in FRS2α^2F/2F mice, in which the Shp2-binding sites of FRS2α are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2α^2F/2F mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2α^2F/2F mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some glomus cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides glomus cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.