Circumventing the blood-brain barrier with autonomic ganglion transplants.

Superior cervical ganglia, whose vessels are fenestrated and permeable to protein tracers such as horseradish peroxidase, were transplanted to undamaged surfaces in the fourth ventricle of rat pup brains. Horseradish peroxidase, infused systemically into the host, was exuded from the graft's vessels into the graft's extracellular stroma within 1 minute. At later times the glycoprotein reached the extracellular clefts of adjacent brain tissue, the vessels of which appeared to retain their impermeability. The blood-brain barrier to horseradish peroxide was thus bypassed where the extracellular compartments of graft and brain became confluent. The graft of autonomic ganglia can serve as a portal through which peptides, hormones, and immunoglobulins may likewise enter the brain.

Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats.

Several putative sources of reactive oxygen species could potentially contribute to diabetic neuropathy and vasculopathy. The aim was to assess the involvement of elevated xanthine oxidase activity. After 6 weeks of streptozotocin-diabetes, groups of rats were given 2 weeks of high-dose allopurinol treatment (50 and 250 mg/kg) to gauge the effect of maximal blockade of xanthine oxidase. In the final experiments, rats were subjected to sensory testing and, under butabarbital anaesthesia, measurements were made on nerve conduction velocities and neural tissue blood flow estimated by hydrogen clearance microelectrode polarography. Further groups were used to study detailed responses of the isolated mesenteric vascular bed after 4 weeks of diabetes and allopurinol (150 mg/kg) treatment. Diabetes caused 20% and 14% reduction in motor and sensory conduction velocity, which were 78% and 81% corrected by allopurinol treatment respectively, both doses giving similar results. Diabetic rats showed tactile allodynia and thermal hyperalgesia, which were completely corrected by allopurinol, whereas mechanical hyperalgesia was only 45% ameliorated. Sciatic nerve and superior cervical ganglion blood flow was halved by diabetes and allopurinol corrected this by approximately 63%. Mesenteric endothelium-dependent vascular responses to acetylcholine, which depend upon nitric oxide and endothelium derived hyperpolarizing factor, were attenuated by diabetes. Allopurinol treatment gave approximately 50% protection for both components. Thus, xanthine oxidase is an important source of reactive oxygen species that contributes to neurovascular dysfunction in experimental diabetes. Inhibition of xanthine oxidase could be a potential therapeutic approach to diabetic neuropathy and vasculopathy.

Distribution of neuropeptide Y Y1 receptors in rodent peripheral tissues.

Using a sensitive immunohistochemical technique, the localization of neuropeptide Y (NPY) Y1-receptor (Y1R)-like immunoreactivity (LI) was studied in various peripheral tissues of rat. Wild-type (WT) and Y1R-knockout (KO) mice were also analyzed. Y1R-LI was found in small arteries and arterioles in many tissues, with particularly high levels in the thyroid and parathyroid glands. In the thyroid gland, Y1R-LI was seen in blood vessel walls lacking alpha-smooth muscle actin, i.e., perhaps in endothelial cells of capillaries. Larger arteries lacked detectable Y1R-LI. A distinct Y1R-immunoreactive (IR) reticulum was seen in the WT mouse spleen, but not in Y1R-KO mouse or rat. In the gastrointestinal tract, Y1R-positive neurons were observed in the myenteric plexus, and a few enteroendocrine cells were Y1R-IR. Some cells in islets of Langerhans in the pancreas were Y1R-positive, and double immunostaining showed coexistence with somatostatin in D-cells. In the urogenital tract, Y1R-LI was observed in the collecting tubule cells of the renal papillae and in some epithelial cells of the seminal vesicle. Some chromaffin cells of adrenal medulla were positive for Y1R. The problem of the specificity of the Y1R-LI is evaluated using adsorption tests as well as comparisons among rat, WT mouse, and mouse with deleted Y1R. Our findings support many earlier studies based on other methodologies, showing that Y1Rs on smooth muscle cells of blood vessels mediate NPY-induced vasoconstriction in various organs. In addition, Y1Rs in other cells in parenchymal tissues of several organs suggest nonvascular effects of NPY via the Y1R.

Identification of prostaglandins in prevertebral venous blood after preganglionic stimulation of the cat superior cervical ganglion.

1. In four out of seven experiments, prostaglandin-like activity was detected in prevertebral venous blood from the superior cervical ganglion, collected during and after preganglionic nerve stimulation.2. Prostaglandins E(1), E(2), F(2alpha) and a prostaglandin A were identified using solvent partition, column and thin-layer chromatography and bioassay techniques.3. The release of PGF(2alpha) was confirmed by combined gas chromatography-mass spectrometry.

Local blood flow and vascular permeability of autonomic ganglion-transplants in the brain.

The purpose of this study was to determine whether the blood vessels of transplanted neural tissue retain their functional characteristics. Quantitative autoradiography was used to measure local blood flow (F) with iodoantipyrine and the blood-to-tissue transfer constant (K) with alpha-aminoisobutyric acid in superior cervical ganglion (SCG) allografted to the surface of ventricle IV and into the cerebellum of the same rat. The F of the intraparenchymal grafts was slightly lower than that of the intraventricular grafts; F decreased between 1 and 4 weeks in SCG grafts at both sites. The permeability-surface area (PS) product of the microvessels and extraction fraction of AIB were calculated from these results and indicated restricted transvascular passage of the amino acid in both the in situ and grafted SCG. Surface area (S) and average length (L) of the microvessels were determined morphometrically and their permeability (P) was calculated from these data. Although K and PS decreased in the grafts compared to in situ SCG, a comparable decrease in S indicated that P was similar for the microvessels of both in situ and 1-week-old SCG transplants: 3.5-4.3 x 10(-6) cm/s. Between 1 and 4 weeks after transplantation, the P of the microvessels decreased to approximately 1.6-2.3 x 10(-6) cm/s without any change in S. Thus, the blood vessels of SCG grafts within or upon the brain initially retain the functional attributes of in situ SCG microvessels, but the average permeability of the graft microvessels decreases to approximately one half of the initial value by 4 weeks after transplantation.

Anatomy and blood supply of the coeliac-superior mesenteric ganglion complex of the rat.

The anatomy of the coeliac-superior mesenteric ganglion (CSMG) complex of 28 female Wistar rats was studied by serial paraffin sections and found to be consistent in composition and in relations. The CSMG comprises tow suprarenal ganglia in continuity with the major splanchnic nerves, these continuing as splanchnic trunks into paired coeliac ganglia. The left coeliac ganglion is larger than the right as it has a superior mesenteric component related to the artery of that name. Lastly, intermesenteric ganglia are related to the renal and ovarian arteries and to the origin of the intermesenteric nerves. Ink injections and microvascular casts indicate that the main extrinsic blood supply to the CSMG is derived from the inferior phrenic artery, a branch of which enters the complex at the suprarenal ganglia and supplies the CSMG via the splanchnic trunks. Also, recurrent branches of the ovarian arteries enter the intermesenteric nerves to supply the complex at its caudal pole. A few small arteries not associated with nerves and probably derived from lumbar arteries also supply the CSMG complex. The two major post-ganglionic nerve trunks have an abundant vasculature in continuity with that of the CSMG but whose origin and direction of blood flow has yet to be determined.

The phrenic ganglion in man.

During educational dissections we observed a phrenic ganglion on the nerve of the phrenic artery originating from the upper pole of the right coeliac ganglion, which accompanied the right inferior phrenic artery on a female cadaver at the age of 34. In our case the left coeliac ganglion, the inferior phrenic artery, the right and left greater, lesser and least splanchnic nerves were present and normal. However, the left nerve of the phrenic artery and the phrenic ganglion were absent. We consider that this rarely reported neural formation may be of importance for anatomists and clinicians.

Blood vessels in ganglia in human esophagus might explain the higher frequency of megaesophagus compared with megacolon.

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.

Blood vessels i ganglia in human esophagus migt explain the higher frequency of megaesophagus compared with megacooon / Vasos sanguíneos em gânglios no esôfago humano poderiam explicar a maior freqüência de megaesôfago comparado com megacolon

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.

Este estudo teve como objetivo avaliar se existem ou não vasos sanguíneos no interior de gânglios do plexo mientérico do esôfago e cólon humano. Foram examinados 15 casos de necrópsias de natimortos, recém-nascidos e crianças de até dois anos de idade, sem alterações gastrintestinais, que faleceram por doenças em outros órgãos. Foram analisados anéis do esôfago e cólon, fixados em formol e processados para inclusão em parafina. Cortes histológicos escalonados foram corados pelas técnicas de hematoxilina-eosina, Giemsa e imuno-histoquímica para caracterização das células endoteliais, utilizando-se os anticorpos anti-fator VIII e CD 31. Foram identificados vasos sanguíneos no interior de gânglios do plexo mientérico do esôfago em todos os casos e não foram vistos vasos sanguíneos em nenhum gânglio do cólon. Concluímos que os gânglios do plexo mientérico do esôfago são vascularizados e, os do cólon, avasculares. A vascularização no interior dos gânglios do esôfago pode facilitar a entrada de agentes infecciosos, bem como o desenvolvimento de respostas inflamatórias (ganglionite) e denervação, como encontrados na doença de Chagas e na acalásia idiopática. Isso pode explicar a frequência maior de megaesôfago comparado com megacólon.

[The effect of gravitational stress in the pelvis--head direction on the blood vessels of the sympathetic trunk]. / Vliianie gravitatsionnykh peregruzok v napravlenii taz--golova na krovenosnye sosudy simpaticheskogo stvola

The experiment was carried out in 15 rabbits. Three of them were control. The stress of the pelvis--head direction was obtained in a centrifuge of 1 m radius. Six animals were rotated for 1 min., the other six--til death, which came within 3--4,5 min. of the experiment. By methods of injection, clearing and measuring it was found that in the vessels of the sympathetic trunk congestion phenomena were first and foremost under effects of stresses of the caudo-cranial direction. Their intensity is in direct dependence on the duration of stress. In the 1st series (1 min.) a considerable congestion of venous blood in the cranial sympathetic ganglion was observed in 1 case, while in the 2nd series (3--4,5 min.) very drastic congestion phenomena, with an enlarged diameter, vein deformity and so on, were constantly noted. A support is given to literature data that such "negative" stresses are less endurable for animals, death comes soon, since the phase of relative compensation under given conditions is promptly changed for the phase of decompensation.

SGC (SIF) cells in autonomic ganglion: evidence for a possible secretion of their content into the blood vessels.

Authors described signs of extrusion of granular vesicles from the SCG (SIF) cells in the inferior mesenteric ganglion of the dog. The granular vesicles were found in extracellular space as well as in the blood capillary lumen. Beside this, large number of granular vesicles were found in the cytoplasm of endothelial cells of blood capillary, mainly in places of close contact between the SGC cell and the endothelial cell of the capillary. These findings strongly suggest secretory function be a primary role of SGC cells in inferior mesenteric ganglion and would explain the rich vascularisation of the SGC cell groups.

[Cytoangioarchitectonics of the parasympathetic ganglion of the frog bladder according to findings from studies during life]. / O tsitoangioarkhitektonike parasimpaticheskogo gangliia mochevogo puzyria prizhiznennykh issledovaniia.

The form of neuronal bodies and their interarrangement with capillaries was studied in prevital parasympathetic ganglia in the bladder of the frog (Rana temporaria). The size of the neurons and the diameter of the capillaries were measured. Most of the neurons were stated to have oval form and they are oriented by their long axis along the capillaries, about 20% neurons have contacts with 2--3 capillaries; some neurons have no contacts and their distance from the nearest capillary is 32--26 mkm. Intermediate structure may be either a connective tissue or neuroglia, or (seldom) other neuronal cells. Unequal conditions of neuronal blood supply, as the author believes, demonstrate their different metabolism and various levels of their functional activity.

Intracellular localization of acetylcholinesterase in nerve terminals and capillaries of the rat superior cervical ganglion.

The ultrastructural localization of acetylcholinesterase (AChE) has been studied in the superior cervical ganglion of the rat. Previous descriptions of the general pattern of localization were confirmed, but in addition, AChE reaction product was found within vesicles in preganglionic nerve terminals, and in pinocytotic vesicles and along the basement lamina of capillaries. There was indication of a continuity between AChE reaction product in the cisternae of the rough endoplasmic reticulum of the principal ganglion cells and extracellular reaction product. These observations are discussed with particular reference to AChE as a secretory protein.

[Differentiated vascularization of the Dogiel cell types and the preferred vascularization of type I cells in the ganglia of plexus submucosus externus (Schabadasch) of the swine]. / Die differenzierte Gefässversorgung der Dogielschen Zelltypen und die bevorzugte Vaskularisation der Typ I-Zellen in den Ganglien des Plexus submucosus externus (Schabadasch) des Schweins.

1. In analyzing the variations in form and density of the periganglionic capillary networks of the plexus Schabadasch there could unequivocally be shown a manifold better vascularisation of type I cell aggregates, compared to those of type II. 2. The preferred vascularisation of type I cells is discussed in relation to the function of the cell types of Dogiel.