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G Gabella

Publications and source records attributed to G Gabella.

At least 19 recordsLinked to original sources
PubMed2000

Growth of nerve fibres into murine peritoneal adhesions.

Adhesions in the peritoneal cavity have been implicated in the cause of intestinal obstruction and infertility, but their role in the aetiology of chronic pelvic pain is unclear. Nerves have been demonstrated in human pelvic adhesions, but the presence of pain-conducting fibres has not been established. The purpose of this study was to use an animal model to examine the growth of nerves during adhesion formation at various times following injury and to characterize the types of fibres present. Adhesions were generated in mice by injuring the surface of the caecum and adjacent abdominal wall, with apposition. At 1-8 weeks post-surgery, adhesions were processed and nerve fibres characterized histologically, immunohistochemically, and ultrastructurally. Peritoneal adhesions had consistently formed by 1 week after surgery and from 2 weeks onwards, all adhesions contained some nerve fibres which were synaptophysin, calcitonin gene-related peptide, and substance P-immunoreactive, and were seen to originate from the caecum. By 4 weeks post-surgery, nerve fibres were found to originate from both the caecum and the abdominal wall, and as demonstrated by acetylcholinesterase histochemistry, many traversed the entire adhesion. Ultrastructural analysis showed both myelinated and non-myelinated nerve fibres within the adhesion. This study provides the first direct evidence for the growth of sensory nerve fibres within abdominal visceral adhesions in a murine model and suggests that there may be nerve fibres involved in the conduction of pain stimuli.

Abdominal Muscles↗
PubMed1999

Structure of the intramural nerves of the rat bladder.

The bladder of adult female rats receives approximately 16,000 axons (i.e., is the target of that many ganglion neurons) of which at least half are sensory. In nerves containing between 40 and 1200 axons cross-sectional area is proportional to number of axons; >99% of axons are unmyelinated. A capsule forms a seal around nerves and ends abruptly where nerves, after branching, contain approximately 10 axons. A single blood vessel is present in many of the large nerves but never in nerves of <600 axons. The number of glial cells was estimated through the number of their nuclei. There is a glial nucleus profile every 76 axonal profiles. Each glial cell is associated with many axons and collectively covers approximately 1, 000 microm of axonal length. In all nerves a few axonal profiles contain large clusters of vesicles independent of microtubules. The axons do not branch; they alter their relative position along the nerve; they vary in size along their length; none has a circular profile. All the axons are fully wrapped by glial cells and never contact each other. The volume of axons is larger than that of glial cells (55%-45%), while the surface of glial cell is twice as extensive as that of axons; there are approximately 2.27 m(2) of axolemma and approximately 4.60 m(2) of glial cell membrane per gram of nerve. Of the mitochondria of a nerve approximately 3/4 are in axons and approximately 1/4 in glial cells.

Animals↗
PubMed1999

Structural changes in the rat bladder after acute outlet obstruction.

The urinary bladder of adult female rats was subjected to complete outlet obstruction for periods of up to 24 h. Within 2 h the obstruction led to a rise in intravesical pressure to about 80 mmH2O. Subsequently, the pressure remained high but declined slightly. After 24 h of complete obstruction the bladder was maximally distended, but its volume was similar to that of a control bladder fully distended, indicating that overstretch (or overdistension) occurs only to a very limited degree. After 6 h of obstruction there was congestion of all the intramural blood vessels and extravasation of red blood cells from some vessels of the mucosa. At 12 h and 24 h the extravasation was very substantial and there was also infiltration of erythrocytes in the muscle layer. Ultrastructurally, there were several damaged nerve endings (but no changes in the nerve trunks) and, occasionally, damaged muscle cells. Removal of the obstruction after 24 h was followed by resorption of the extravasate, partly by phagocytosis by muscle cells, a process which lasted 4-6 days, and by 7 days damaged varicosities and muscle cells became uncommon. We conclude that the changes observed in the bladder wall following complete obstruction are caused more by haemorrhage and ischaemia than by overstretch and that the changes are reversed when outlet conditions are normalized.

Acute Disease↗
PubMed1999

[Molecular and cellular determinants of arterial stiffness: role of cell-matrix connections].

Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.

Animals↗
PubMed1998

Glial fibrillary acidic protein (GFAP) immunoreactivity in enteric ganglia of the chick embryo.

We examined by immunohistochemistry the expression of glial fibrillary acidic protein (GFAP) in enteric ganglia of the chick embryo, using a polyclonal antibody. The morphology of enteric ganglion cells was examined by electron microscopy. Faint GFAP immunoreactivity was detected in ganglion cells and cell processes from around day 7 in ovo. Later in development the intensity of the immunofluorescence increased and it became more evident that immunoreactive small ganglion cells (interpreted as primitive glial cells), and their processes, surrounded larger negative cell profiles (interpreted as primitive neuronal cells); GFAP immunofluorescence was also evident in intramuscular and mucosal nerve trunks. In colocalization experiments, GFAP immunoreactivity was detected in a proportion of HNK-1/N-CAM immunoreactive ganglion cells, in both the myenteric and submucosal plexus. In addition, we observed GFAP immunoreactive nerves in wholemount preparations of chick gut from as early as day 4.5 in ovo. In the ganglionated nerve of Remak, GFAP immunoreactive satellite and Schwann cells were in evidence from day 5 of incubation. Neuronal markers, such as neurofilament, have been detected very early in development in neural crest cell populations in chick enteric ganglia. In contrast, the expression of markers of the glial phenotype has previously been observed only in the late stages of embryonic development. From our experiments, we conclude that neuronal and glial phenotypes are immunohistochemically distinct from as early as day 4.5 of incubation, even if by ultrastructural criteria glial cells are clearly distinguishable from neurons only after day 16 in ovo.

Animals↗
PubMed1998

The distribution of intramural nerves in urinary bladder after partial denervation in the female rat.

We evaluated the degree of neuronal plasticity following a partial denervation of the rat urinary bladder. Using acetylcholinesterase staining we found that the postganglionic nerves from the pelvic ganglion reach the intact bladder as 1-4 nerve trunks on each side, slightly ventral and caudal to the ureteral orifices. Normally a few thinner nerves also reach the bladder posterolateral to the ureterovesical junction. The nerves ventral to the ureters run in the ventral longitudinal muscle layer as well-defined trunks with a pattern that does not differ much from one animal to another. The nerves reaching the bladder dorsolaterally innervate the dorsolateral aspects in a more irregular fashion. Some anastomoses are found across the midline between nerves from either side. This nerve pattern is already in place in newborn rats. After removal of the pelvic ganglion on one side in the adult rat the ipsilateral ventral nerves rapidly degenerate, whereas some dorsolateral nerves usually survive. Axons from the intact ventral nerves can be seen crossing over to the denervated side in the anastomoses. After 13 weeks the surviving ventral nerves, which normally run at some distance from the ventral midline, now run in the midline with equal amounts of ventral longitudinal muscle on either side, and with their branches evenly distributed to both sides. The same pattern is seen after 27 weeks. Unilateral ganglionectomy in 3-week-old rats leads to the same changes in nerve distribution as in the adult rat. We conclude that there is a high degree of plasticity in the bladder innervation following a partial denervation, and that this plasticity includes the distribution of its main intramural nerve trunks.

Acetylcholinesterase↗
PubMed1998

Homotransplant of pelvic ganglion into bladder wall in adult rats.

In these experiments a large portion of the pelvic ganglion of adult female rats was transplanted into the wall of the urinary bladder of the same animals. The morphology and fine structure of the transplants were studied in whole-mounts and in sections for light and electron microscopy, from two days up to four months after operation. The general architecture of the ganglion was preserved in all the transplants. The vascularization was re-established. Nerves grew out of the transplant and connections with the original intramural nerves of the bladder wall were established. All the synapses degenerated at the time of transplantation; new synapses began to reappear on the ganglion neurons in the oldest transplants. Although some neurons in the transplant degenerated during the first few days, the majority of neurons survived for the full length of the experiments (four months). Satellite glial cells and small intensely fluorescent cells had a similar structure and distribution as in control ganglia. The results show that the homotransplant of pelvic neurons into the bladder has a high rate of success, in terms of survival, maintenance of fine structure, growth and re-connections; these neurons of adult organisms display plastic and regenerative abilities.

Acetylcholinesterase↗
PubMed1998

Distribution of afferent axons in the bladder of rats.

The distribution of afferent axons in the bladder of rats was studied by means of immunohistochemistry for calcitonin gene-related peptide (CGRP), in frozen sections and in wholemount preparations of mucosa and muscle coat. Synaptophysin-immunofluorescence was used for the general detection of all intramural axons. The afferent axons were distributed over four distinct targets: at the base of the epithelium, inside the epithelium, on blood vessels (both arteries and veins) and along muscle bundles. In the mucosa, all the afferent axons, except the perivascular ones, lay either inside the epithelium or in a subepithelial plexus very close to the basal surface of the epithelium. The plexus was thickest in the neck of the bladder and in the initial portion of the urethra, and it became progressively less dense in the adjacent regions; it did not extend beyond the equatorial region, and therefore the mucosa of the cranial region of the bladder had no afferent axons. Most of the axons in the subepithelial plexus were terminal axons and included conspicuous varicosities arranged in very long chains; branching points were numerous, usually at right angles and located at the level of a varicosity; some axons split and then rejoined, forming closed axonal loops. The afferent innervation of the musculature was more diffuse, and appeared uniform throughout the bladder. After unilateral surgical denervation (by excision of the pelvic ganglion 5-7 days earlier) areas of complete denervation were observed, but there were large areas where the innervation was only reduced. The results showed that there is a bilateral innervation of many regions of the mucosa and the musculature, including individual muscle bundles. A substantial number of fibres crossed the midline into the contralateral side of the bladder. CGRP-immunofluorescence in mucosal afferent axons is enhanced in the surviving axons 5 days after contralateral denervation, a change which is interpreted as an early sign of regeneration.

Afferent Pathways↗
PubMed1998

Connection of smooth muscle cells to elastic lamellae in aorta of spontaneously hypertensive rats.

We have recently demonstrated that in large arteries of spontaneously hypertensive rats (SHR), there is no increase of stiffness despite the increase in wall thickness, a sign of mechanical adaptation of the arterial wall to the higher level of stress. Because the dense plaques of smooth muscle are a major site of anchorage between the muscle cells and extracellular matrix, we determined by electron microscopy the distribution of dense plaques and their connections to elastic lamellae in the abdominal aorta of 1-year-old SHR and control Wistar rats. In vivo echo-tracking measurement of aortic distensibility and elastic modulus indicates a reduction of arterial stiffness in SHR compared with Wistar rats when they are studied over a common range of blood pressure. The media thickness to body weight ratio was higher in SHR than in Wistar rats. In the media, the percentage of sectional area occupied by extracellular matrix was not different between Wistar rats and SHR. The average number of dense plaques per muscle cell was not different between Wistar rats and SHR. However, the percentage of cell surface occupied by dense plaques was increased in SHR, and the percentage of cell surface connected to the elastic lamellae was twice as high in SHR compared with Wistar rats (9.4+/-1.5% versus 3.8+/-1.1%). These results suggest that the elastin network plays a major role in the mechanical adaptation of the arterial wall in SHR, not through variations of its total amount but through variations of the extent of anchorage to the muscle cells.

Adaptation, Physiological↗
PubMed1997

Laminin immunoreactivity in enteric ganglia of the chick embryo.

The localization and time of appearance of laminin in the duodenum of the chick embryo were studied with an anti-laminin polyclonal antibody and immunofluorescence. Laminin immunoreactivity was observed in the basement membranes of the mesothelium, mucosal epithelium, muscle cells and in the adventitia and basal surface of the endothelium in blood vessels. In addition, laminin immunostaining was detected over the contour of myenteric ganglia from embryonic day 7 and inside these ganglia from embryonic day 13. In colocalization experiments, laminin immunoreactivity occurred outside tubulin immunoreactive neuronal cell bodies, thus indicating that it resides in glial cells or in extracellular spaces. In addition connecting strands of the myenteric plexus and intramuscular nerves expressed laminin immunoreactivity. Similar observations were made in the proventriculus, gizzard, ileum and rectum of chick embryos, and in the duodenum and rectum of quail embryos. In the ganglion of Remak, laminin immunofluorescence was detected in the collagenous sheath that surrounds the ganglion and inside the ganglion, where it outlines neuronal cell bodies. Laminin immunoreactivity within the myenteric ganglia during the 3rd week in ovo, appears to be characteristic of the avian species examined, since it was not observed in the rat and mouse intestine at equivalent developmental stages. Immunocytochemical experiments at the electron-microscope level confirmed that structures with laminin or laminin-like immunoreactivity occur both around and inside myenteric ganglia. It is suggested that laminin, or an immunologically similar molecule, may play a role in the development and maturation of avian enteric ganglia.

Animals↗
PubMed1996

Decrease and disappearance of intramural neurons in the rat bladder during post-natal development.

While confirming previous results that the bladder of adult female rats is devoid of intramural neurons, we show that during postnatal development some intramural neurons are present. There is about 200 of them per bladder at birth, and their number progressively decreases during post-natal life. In this strain of rats some neurons are still present at 12 weeks of age, and in one animal (out of five) there were still 25 neurons at 20 weeks of age.

Animals↗
PubMed1996

Origin of the c-kit-positive interstitial cells in the avian bowel.

Interstitial cells of Cajal (ICC) aroused much interest among neuroanatomists at the beginning of the century. These small cells, organized into networks, are intercalated between nerve fibers and muscle cells, and are now considered by many authors to be responsible for the pacemaker activity of the gut. Renewed interest in these cells arose recently when the receptor tyrosine kinase, c-kit, was shown to be associated with their functional activity. The embryonic origin of interstitial cells has remained a controversial issue ever since their discovery. Some authors consider them to be of neural or glial nature and thus of neural crest origin. Others consider them to be of fibroblastic or muscular nature. We have applied the quail-chick marker system to solve this problem. ICC were identified by means of a chicken-c-kit nucleic probe which cross-reacts with the quail c-kit gene product. We constructed chimeric bowels by grafting isotopically quail vagal neural crest into chick embryos at embryonic day 2 (E2). The enteric innervation of the chimeras was then of quail origin. In situ hybridization of the chimeric bowels showed that all the c-kit-positive cells were of the chick type, and therefore belonged to the gut mesenchyme and were not neural crest-derived cells. This observation was confirmed by culturing aneural chick guts on the chorio-allantoic membrane. Typical ICC, as defined at the EM level and by their expression of the c-kit receptor, developed in the gut wall in the complete absence of enteric innervation. One can conclude the ICC are of mesodermal origin and develop independently from enteric neurons with which they later establish anatomical and functional relations.

Animals↗
PubMed1995

Intramural neurones appear in the urinary bladder wall following excision of the pelvic ganglion in the rat.

The entire bladder of female rats was stained for acetylcholinesterase activity, in order to make visible all the intramural nerves. Ganglion neurones were never observed within the bladder wall of adult controls. In contrast, 2, 13 or 27 weeks after unilateral pelvic ganglion destruction a few intramural neurones were consistently observed along the remnants of nerves in the originally denervated half of the bladder. These neurones were often gathered into clusters of 5-15, inside a nerve or closely connected to it, with a faintly stained nerve leading to them and a more heavily stained nerve leading from them. The origin of the new intramural ganglion neurones is unknown, but they probably migrate after ganglionectomy, possibly from some accessory ganglion close to the bladder.

Acetylcholinesterase↗
PubMed1995

Complex structure of the common carotid artery of sheep.

BACKGROUND: Mechanical properties of blood vessels are dictated by the vessel wall structure. In many large conduit vessels the tunica media is a sheath of circular musculature and the tunica adventitia a layer of fibrous connective tissue with limited longitudinal extensibility. In contrast, the carotid artery of the sheep displays in each tunica a more complex architecture of muscle and connective tissue. METHODS: Vessels collected from ewes were measured and processed for light microscopy and for transmission electron microscopy. RESULTS: Layers of histologically different materials are found within the tunica intima, media and adventitia. (1) The tunica media is made of circumferentially arranged muscle cells markedly different at different depths. In the innermost third of the media, muscle cells are small and with irregular profiles, the cells are widely separated, and the extracellular material is abundant and composed mainly of elastic fibres. In the outermost third, muscle cells are larger and with more regular profiles, the cells are relatively close to each other and the extracellular material is sparse and consists mainly of collagen fibrils. (2) A small number of fibroblasts is found in all parts of the media amongst the preponderant muscle cells. (3) The intima contains fibroblast-like cells and longitudinally arranged muscle cells. (4) The adventitia contains a thick layer of collagen and elastic fibres; external to this, it displays a conspicuous musculature, made of large bundles of longitudinal muscle. CONCLUSIONS: The carotid artery of the sheep presents in all three coats of its wall features which are at variance from those in the better known vessels of small laboratory animals. The presence of many layers of material within the wall, the heterogeneity of the tissues found, and the occurrence of an extensive longitudinal musculature, have important effects on the mechanical properties of the vessel.

Animals↗
PubMed1995

The structural relations between nerve fibres and muscle cells in the urinary bladder of the rat.

Intramuscular nerve fibres in the bladder of adult female rats were investigated by means of serial sections. The following observations were made. (1) Upon penetrating into the musculature the nerve bundles branch repeatedly, and almost all turn into single fibres; their axons become varicose, the Schwann cell sheath is attenuated, incomplete or absent, and the separation between axonal membrane and muscle cell membrane is reduced to tens of nanometres. (2) All single axons, and some of those within bundles, are varicose, but the characteristic of being varicose is expressed by degrees, and is not an all-or-none state. (3) Varicosities contain vesicles (mostly of the agranular type), microtubules (with little connection with the axolemma or the vesicles), some neurofilaments (scarce or absent in the best developed varicosities), mitochondria (whose size is on average smaller than those of the perikaryon, and a minute amount of endoplasmic reticulum. (4) Terminal varicosities, the true anatomical ending of an axon, are often devoid of Schwann cell sheath, are packed with vesicles, rarely contain microtubules or neurofilaments, and lie close to a muscle cell: the gap is often reduced to approximately 10 nm. (5) Schwann cells accompany the axons within the muscle strands. Unlike the area of the axonal profiles, the area of glial sheath changes little along the length of the nerve fibre, except towards its end. (6) The Schwann cell sheath around a varicosity is often incomplete; the area of the axolemma thus exposed is covered by the basal lamina, and is here referred to as a 'window'. While some varicosities have a window only a few tens of nanometres in width, others have more than one window, and some are devoid of Schwann cell altogether, so that their entire axolemma is in contact with the basal lamina. The Schwann cell never extends beyond the axon, whereas very often (and possibly always) the axon extends beyond the Schwann cell. (7) Intervaricose segments vary in length and diameter, the narrowest ones accompanying the more clear-cut varicosities. Some intervaricose segments are as small as 50 nm in diameter, contain a single microtubule and lack a Schwann cell sheath. Others, sheathed by a Schwann cell, contain a single neurofilament or no organelles at all.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Reversal of muscle hypertrophy in the rat urinary bladder after removal of urethral obstruction.

We studied the ultrastructure of the bladder musculature after first inducing hypertrophy by means of urethral obstruction and subsequently removing the obstruction. With hypertrophy the bladder musculature increases ten-fold or more in volume; after de-obstruction approximately 4/5 of the hypertrophic muscle weight and volume is lost within six weeks. In spite of this very large decrease in muscle mass there is no degeneration of muscle cells or nerve endings or of other cell types in the de-obstructed bladder either at 5 days or at 6 weeks. The individual muscle cells are smaller in size than in the hypertrophic bladder but still larger than control muscle cells. The decrease in muscle cell size is more substantial than the decrease in muscle cell surface. There are no lysosomes or other signs of intracellular degradation in any cells of the muscle layer. The musculature contains a very large amount of intercellular material, mainly collagen. This study documents the great plasticity of the musculature in the reduction of muscle mass after de-obstruction. However, some of the fine structural features are almost as different from the controls as in the hypertrophic muscle.

Animals↗
PubMed1993

Effect of decentralization or contralateral ganglionectomy on obstruction-induced hypertrophy of rat urinary bladder muscle and pelvic ganglion.

After urethral obstruction the musculature of the rat urinary bladder undergoes extensive hypertrophy, irrespective of whether its innervation is intact or whether one of the two pelvic ganglia has been decentralized or excised. Even the excision of both ganglia does not inhibit muscle hypertrophy. The presence of nerves is not a prerequisite for the muscle growth to occur. The stimulus for growth resides in the bladder itself, and the present and previous observations are in agreement with the notion that the distension of the muscle is a primary stimulus for muscle growth. With bladder hypertrophy, the pelvic ganglion neurons undergo hypertrophy, even when they are devoid of their preganglionic input. Synaptic connection with the preganglionic fibres and stimuli from the spinal cord are not prerequisites for neuronal hypertrophy. However, the hypertrophy is less marked in the decentralized ganglion neurons than in the neurons of the contralateral intact ganglion. With bladder hypertrophy and contralateral ganglionectomy, the neuronal hypertrophy is greater than with either procedure alone, suggesting that the two forms of neuronal growth stimulation can be added to each other.

Animals↗