Anatomical map of the cranial vasculature and sensory ganglia.

There is growing evidence of a direct influence of vasculature on the development of neurons in the brain. The development of the cranial vasculature has been well described in zebrafish but its anatomical relationship with the adjacent developing sensory ganglia has not been addressed. Here, by 3D imaging of fluorescently labelled blood vessels and sensory ganglia, we describe for the first time the spatial organization of the cranial vasculature in relation to the cranial ganglia during zebrafish development. We show that from 24 h post-fertilization (hpf) onwards, the statoacoustic ganglion (SAG) develops in direct contact with two main blood vessels, the primordial hindbrain channel and the lateral dorsal aortae (LDA). At 48 hpf, the LDA is displaced medially, losing direct contact with the SAG. The relationship of the other cranial ganglia with the vasculature is evident for the medial lateral line ganglion and for the vagal ganglia that grow along the primary head sinus (PHS). We also observed that the innervation of the anterior macula runs over the PHS vessel. Our spatiotemporal anatomical map of the cranial ganglia and the head vasculature indicates physical interactions between both systems and suggests a possible functional interaction during development.

Local blood flow in peripheral nerves and their ganglia: Resurrecting key ideas around its measurement and significance.

Over 3 decades ago, seminal work by Phillip Low and colleagues established exquisite physiology around the measurement of nerve blood flow (NBF). Although not widely explored recently, its connection to the clinic has awaited human methodology. While human studies have not achieved a convincing level of rigour, newer imaging technologies are offering early information. The peripheral nerve trunk has parallel blood flow compartments that include epineurial flow dominated by arteriovenous shunts and downstream endoneurial blood flow (EBF). NBF and EBF have lower values than central nervous system blood flow, lack autoregulation yet have sympathetic and peptidergic neurovascular control. Contrary to expectation, injury to nerves is often associated with rises in NBF rather than ischemia, a finding of biological interest corroborated by human studies. Despite its potential importance, quantitative human measurements of EBF and NBF are not yet available. However, with development, careful NBF analysis may present new insights into nerve disorders. Muscle Nerve 57: 884-895, 2018.

Antagonism of ionotropic glutamate receptors attenuates chemical ischemia-induced injury in rat primary cultured myenteric ganglia.

Alterations of the enteric glutamatergic transmission may underlay changes in the function of myenteric neurons following intestinal ischemia and reperfusion (I/R) contributing to impairment of gastrointestinal motility occurring in these pathological conditions. The aim of the present study was to evaluate whether glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R. Primary cultured rat myenteric ganglia were exposed to sodium azide and glucose deprivation (in vitro chemical ischemia). After 6 days of culture, immunoreactivity for NMDA, AMPA and kainate receptors subunits, GluN(1) and GluA(1-3), GluK(1-3) respectively, was found in myenteric neurons. In myenteric cultured ganglia, in normal metabolic conditions, -AP5, an NMDA antagonist, decreased myenteric neuron number and viability, determined by calcein AM/ethidium homodimer-1 assay, and increased reactive oxygen species (ROS) levels, measured with hydroxyphenyl fluorescein. CNQX, an AMPA/kainate antagonist exerted an opposite action on the same parameters. The total number and viability of myenteric neurons significantly decreased after I/R. In these conditions, the number of neurons staining for GluN1 and GluA(1-3) subunits remained unchanged, while, the number of GluK(1-3)-immunopositive neurons increased. After I/R, -AP5 and CNQX, concentration-dependently increased myenteric neuron number and significantly increased the number of living neurons. Both -AP5 and CNQX (100-500 µM) decreased I/R-induced increase of ROS levels in myenteric ganglia. On the whole, the present data provide evidence that, under normal metabolic conditions, the enteric glutamatergic system exerts a dualistic effect on cultured myenteric ganglia, either by improving or reducing neuron survival via NMDA or AMPA/kainate receptor activation, respectively. However, blockade of both receptor pathways may exert a protective role on myenteric neurons following and I/R damage. The neuroprotective effect may depend, at least in part, on the ability of both receptors to increase intraneuronal ROS production.

Injury to myenteric plexus of intestinal segments after vascular pedicle interruption: an experimental study in rats and rabbits.

A study was conducted in rats and rabbits to histologically evaluate the effect of acute and late interruption of blood supply on the myenteric plexus located between the circular and longitudinal layers of the muscularis externa (Auerbach's plexus). An intestinal segment measuring 2 cm in rats and approximately 8cm in rabbits was sectioned and isolated on a mesenteric vascular pedicle. Animals in Group underwent clamping of the vascular pedicle for 1, 2, 3, 4, 5 or 6 h. There were 5 animals in each of these subgroups. Group: Intestinal segments with intact vascular pedicles were transferred from the abdominal cavity into the subcutaneous space. Groups with 5 animals in each underwent pedicle ligation immediately and at 1, 2, 3 or 4 weeks after the first operation. Three days later, histological studies were carried out. Injury to the myenteric plexus and the longitudinal muscle was observed in the viable intestinal segments when the mesenteric vascular pedicle was clamped for 4 to 5 h. Similar findings were observed when the pedicle was ligated within 1 to 2 weeks after grafting. The present results show that ischemia can cause injury to the myenteric plexus in the surviving intestine.

[Ultrastructural bases of microcirculatory disorders in intraganglionic capillaries and disorders of nerve elements in the small intestine of suckling rabbits in experimental cholera]. / Ul'trastrukturnye osnovy mikrotsirkuliatornykh rasstroistv v intraganglionarnykh kapilliarakh i narushenii nervnykh élementov tonkoi kishki krolikov-sosunkov pri éksperimental'noi kholera.

The 10-12-day suckling rabbits received culture of V. el tor into the stomach, and the ultrastructural changes of intraganglionic capillaries and nervous elements of small intestine were studied in the course of experimental cholera. It was established that the initial changes 1.5 hrs after the beginning of the experiment were characterized by permeability increase, thrombohemorrhagic syndrome development, oedema of endotheliocytes and perivascular space, fibrin precipitation. There were reactive changes in neurons, but alterations in synapses were absent. In the period of cholera vibrio adhesion (4 hrs) the new signs of endothelial cells desquamation developed. At the same time haemorrhages became more distinct and cells of extravasates more diverse. The development of experimental cholera (1-2 days) was accompanied by appearance of large numbers of coated vesicles in endothelium, tight junctions damage and endothelial cells destruction, extensive dysendothelization which promoted blood cells contact with collagen. In this period dystrophic changes progressed in neurons and activation of cholinergic synapses took place. Enhancement of transepithelial transport of liquid, induced by cholera toxin, is partly connected with activation of cholinergic mechanisms in autonomic ganglia of the small intestine.

Ultrastructural studies on the barrier properties of the paraganglia in the rat recurrent laryngeal nerve.

The permeability of blood capillaries in the paraganglia of the rat recurrent laryngeal nerve (RLN) was investigated by employing the ionic lanthanum tracer at ultrastructural level. Two types of blood capillaries, namely, fenestrated and nonfenestrated types, were observed in the rat RLN and its associated paraganglia (RLN paraganglia). A preferential distribution of fenestrated capillaries in the RLN paraganglia was noted. Nonfenestrated capillaries were distributed in the area of RLN devoid of paraganglia. Minute aberrant ganglia consisting of 4-8 neurons were frequently encountered in the rat RLN near the paraganglia. The capillaries in these neuronal areas were also nonfenestrated. The lanthanum tracer was limited within the vascular lumen, but not in the extravascular space, in the RLN proper and in the area of RLN paraganglia where the neurons were identified. In the RLN paraganglia, the tracer was located in the vascular lumen, extravascular space, periaxonal space of nerve fibers, and the intercellular space of the RLN paraganglionic cells. We concluded that (1) a blood-nerve barrier and a blood-ganglion (or blood-neuron) barrier exist in the area of RLN devoid of paraganglia, and (2) blood-paraganglion barrier and blood-nerve barrier were lacking in the rat RLN paraganglia.

Isolated bowel segment (Iowa Model 1): technique and histological studies.

An isolated bowel segment (IBS) is a viable loop of bowel that is completely free of its mesenteric attachments. We created an IBS by staged procedures: (1) myoenteropexy between the undersurface of the abdominal wall muscle and a jejunal loop that is exteriorized at both ends as mucous fistulae; and (2) division of the IBS mesentery several weeks later. Viability of the IBS is preserved by vascular collaterals that develop at the myoenteropexy during the interval between these two procedures. In this study, histological observation of the IBS was performed to retrospectively determine the optimal interval required for adequate collateral circulation to develop. Twenty-eight rats were subdivided into seven groups of four rats each; each group underwent mesenteric division of the IBS at successive 1-week intervals after myoenteropexy (1 to 7 weeks). The bowel wall structures were histologically examined under light microscopy for each group after mesenteric division. Ischemic changes were observed in the groups in which the intervals were shorter than 6 weeks. With the time interval longer than 6 weeks, no ischemic changes were observed in the intramural ganglia and muscle layers and minimal changes were noted in the mucosa. This study concluded that an IBS can be safely created in the rat that preserve normal bowel structures when its mesentery is divided 7 weeks after myoenteropexy.

Ganglionic circulation and its effects on neurons controlling cardiovascular functions in Aplysia californica.

The abdominal ganglion of the mollusk Aplysia californica receives most of its blood supply through a small caudal artery that branches off the anterior aorta near its junction with the heart. Injection of an ink/gelatin mixture into the caudal artery revealed a consistent pattern of arterial branching within the ganglion and a general proximity of larger vessels to identified neurons controlling circulation in this animal. This morphological arrangement was particularly evident for the heart excitor interneuron, cell L10, which lies next to the caudal artery near its entry into the ganglion. In electrophysiological experiments, L10 was excited when blood flow or oxygen tension within the ganglion was reduced. This effect was expressed as a gradual increase in impulse frequency of L10 and conversion from tonic to bursting mode of spike discharge. L10 follower cells in the RB and LD neuron clusters were affected synaptically by the changes in L10 activity, while other follower cells (L3 and RD neurons) responded independently of L10's synaptic influence. The neurosecretory white cells (R3 to R14) that innervate the major arteries and pericardial tissues were also excited when ganglionic circulation was interrupted. In innervated preparations of the heart and respiratory organs, decreased circulation through the abdominal ganglion stimulated a transient increase in the rate and amplitude of respiratory (gill) pumping and pericardial contractions and caused a sustained increase in activity of the heart. Both responses increase cardiac output and both appear to involve a direct influence of ganglionic circulation on interneurons controlling the gill and heart. These results indicate that the cell-specific patterns of excitation and inhibition caused by fluctuations in ganglionic circulation may be important factors for maintaining circulatory homeostasis in this animal.

[Organogenesis of cranial ganglia in the chick embryo: a comparison of the development of blood vessels and neurocytodifferentiation]. / L'organogenesi in gangli encefalici dell'embrione di pollo : confronto tra sviluppo dei vasi sanguiferi e neurocitodifferenziazione.

Neurohistogenetic and vasculogenetic processes have been analytically compared in several cranial ganglia, ciliary (III nerve), semilunar (V nerve), vestibulocochlear (VIII nerve), petrosal (IX nerve) and nodose (X nerve), of chicken embryos from the 3rd to the 12th incubation day. The results indicate that during the organogenesis of these ganglia the formation of the first intrinsic vessels and the successive development of vascular networks follow the beginning and, respectively, the main steps of the neuroblast morphological maturation. The differences noticed by the Authors as concerns the chronological sequence showed by the vasculogenetic events in the various ganglia have been ascribed to the different proceeding of the neurohistogenesis since blood vessels first appear and build networks where the ganglionic development and differentiation are more precocious.

[Vascularization of the plexus myentericus (Auerbach) in the small intestine of swine and cats]. / Die Gefässversorgung des Plexus myentericus (Auerbach) im Dünndarm von Schwein und Katze.

The ganglia of the plexus myentericus (Auerbach) have their own self-acting vascularization in the form of periganglionic capillary networks. As to the architecture and density, they are quite different from the intramuscular capillary bed. Just as the arterial trunk and arcade vessels, the terminal arterioles and sphincter capillaries running into the periganglionic cappillary network are innervated by noradrenergic axons. Together with periganglionic arteriovenous short circuits, this means favorable prerequisites for a functionally adapted blood supply of the ganglia. The specific arrangement of intramuscular vessels and the plexus Auerbach effects the maintenance of the close topographic and functional relations between both systems in all cases of changes of the shape of the intestinal wall.

[Vascularization of plexus myentericus (Auerbach) in the large intestine of the cat]. / Zur Gefässversorgung des Plexus myentericus (Auerbach) im Dickdarm der Katze.

1. Coincidental preparation of the intramuscular vascular bed and the plexus myentericus (Auerbach) of the cat's large intestine by India-ink method and silverimpregnation allowed to demonstrate independent vascularisation of ganglia and nerve-branches of the plexus Auerbach. 2. Each ganglion is surrounded by a capillary network widely independently existing of the intramuscular capillary bed. The preferred innervated terminal arterioles and especially the sphincteric capillaries opening into the periganglionic capillary network and the numerous arterio-venous short-circuits in its marginal area suggest to conclude a differentiated regulation of blood supply.

Sensitivities of ocular tissues to acute pressure-induced ischemia.

Intraocular pressure was artificially elevated for eight hours in eight owl monkeys. The first permanent effect (produced at a perfusion pressure of plus 15 mm Hg) was partial necrosis of iris stroma and ciliary processes, associated with microscopic lesions in the photoreceptors and retina pigment epithelium around the disc and in the retinal periphery. At a slightly higher pressure, visual nerve fibers in the retina and optic nerve and their ganglion cells were affected. Simultaneously, the outer retinal layers showed damage to the pigment epithelium, photoreceptors, and other nuclear layers. At even higher pressures, nearly all the other intraocular tissues were affected except for Müller cells, astroglia in the optic nerve head, epithelium of the pars plana, and the pigment cells of the choroid. The possibility is raised of a nonischemic pressure-induced mechanism for destruction of disc astrocytes in human chronic glaucoma.