Cholinergic innervation in the human striatum: a three-compartment model

The mammalian striatum is divided into compartments that are anatomically and neurochemically distinct. The dorsal striatum has been described as containing two compartments, striosomes and matrix, while the ventral striatum is thought to have a more complex, multi-compartmental organization. In this study, we sought to characterize the compartmentalization of the dorsal and ventral portions of the human striatum using choline acetyltransferase as a marker. Image analysis was used to assess relative densities of immunostaining, and three distinct, choline acetyltransferase-immunostained compartments were demonstrated: intensely immunostained, moderately immunostained and weakly immunostained areas. The dorsomedial portion of the striatum was made up of moderately immunostained regions embedded within a densely immunostained background, thus manifesting the characteristic striosome/ matrix organization of the dorsal striatum. However, the ventral and lateral two-thirds of the striatum were made up of a mixture of densely immunostained, moderately immunostained and weakly immunostained areas, with the moderately immunostained region forming the bulk of the background tissue, and smaller, densely immunostained and weakly immunostained regions embedded within it. These compartments were compared to regions defined by distinct levels of acetylcholinesterase immunostaining in adjacent sections; the staining patterns produced by the two cholinergic markers were found to be identical except in some portions of the nucleus accumbens, where acetylcholinesterase immunostaining was found to be more intense than choline acetyltransferase immunostaining. The immunoreactive somata were mapped within sections stained for choline acetyltransferase taken from different rostrocaudal levels of the striatum, and the distributions and densities of immunoreactive somata within these three cholinergic compartments were determined. In general, the densities of cholinergic somata roughly correlated with immunostaining intensity of regions, e.g. the most intensely immunostained compartment also had the highest densities of cholinergic somata. However, in the rostroventral striatum, the densities of cholinergic somata in the weakly immunostained compartment roughly equalled the densities of cholinergic somata in the moderately immunostained compartment, suggesting that local axonal arborizations of cholinergic cells may differ in density or orientation between the two compartments, or, alternatively, that some of the cholinergic cells in the weakly immunostained compartment may project outside of the striatum. The large proportion of striatum displaying ventral striatal characteristics (a complex, multi-compart-mental organization) in humans relative to that observed in other mammals suggests that the role of the ventral striatum may be expanded and more highly differentiated in the human brain.     

Histophysiologic characteristics of the effector innervation of the arteries of the base of the brain during rat ontogenesis

The development of adren- and cholinergic nervous plexuses in the brain base arteries was studied by histochemical methods of Falck and Kelle in animals and fetuses of 10-22 days, newborn rats, animals of 10, 20, 30, 40, 60 and 120 days of life and 1 and 2 years old rats. The cholinergic nerve fibres were first found in the basilar, vertebral and internal carotid arteries on the 15th and 16th days of ontogenesis. Specific fluorescence of adrenergic conductors on the same arteries is revealed somewhat later--from the 17th and 18th days of the intrauterine development. Further formation of the cholin- and adrenergic innervation of the arteries of the Willis' circle goes on synchronously. The number of nerve fibres increases with the growth of the artery diameter. The concentration of catecholamines and the activity of AChE in them gradually increases. The greatest density of nerve fibres per 1 mm2 is determined in 20-day-old rats. The number of cholinergic nerve fibres on the arteries of the brain base is equal to that of adrenergic fibres during the whole period of postnatal ontogenesis. By the 30th day the effector nervous apparatus has a definite structure. In old rats the activity of AChE and the content of catecholamines drop, the amount and concentration of nerve fibres decrease.     

A histochemical study of the innervation of cerebral blood vessels in the snake

Dual innervation of snake cerebral blood vessels by adrenergic and cholinergic fibres was demonstrated with the use of histochemical methods. Although the nerve plexuses are somewhat less dense, the essential features of innervation of the blood vessels are similar to those of mammals with the exception that the adrenergic plexuses are more prominent than the cholinergic plexuses. The major arteries of the cerebral carotid system have a rich nerve supply. However, the innervation is less rich in the basilar and poor in the spinal (vertebral) arteries. Although the arteries supplying the right side of head are poorly developed, three pairs of arteries, cerebral carotids, ophthalmics and spinals, supply the snake brain. The carotids and ophthalmics are densely innervated and are accompanied by thick nerve bundles, suggesting that the nerves preferentially enter the skull along those arteries. Some parenchymal arterioles are also dually innervated. Connection between the brain parenchyma and intracerebral capillaries via both cholinergic and adrenergic fibres was observed. In addition cholinergic nerve fibers, connecting capillaries and the intramedullary nerve fibre bundles, were noticed. Capillary blood flow may be influenced by both adrenergic and cholinergic central neurons. The walls of capillaries also exhibit heavy acetylcholinesterase activity. This may indicate an important role for the capillary in the regulation of intracerebral blood flow.     

The participation of the celiac plexus in the innervation of the bronchi and pulmonary vessels

Nerves and receptors of the bronchial and vascular walls have been studied in dogs, cats and rabbits after extirpation of the celiac plexus, subdiaphragmatic vagotomy and cutting the celiac plexus under the diaphragm. In all the animals operated on and sacrificed 16 h-9 days later, besides intact nerves, there were many neural fibres and receptors reactively and destructively changed. Some neural elements were at the state of Waller's decomposition. Owing to the data obtained, it is possible to conclude that the celiac plexus and the abdominal part of the vagus nerve and that of the celiac nerve participate in innervation of the bronchi and the pulmonary vessels.     

The participation of mast cells and serotonin-immunoreactive fibers in the innervation of the cerebral vessels

Interrelations between adrenergic and serotoninergic nerve fibres and mast cells located near the vascular wall were studied on total preparations of rat brain pia mater. Histochemical method with glyoxylic acid revealed the dense network of adrenergic fibres and their terminal regions with variceal endings with mast cells located next to them. Immunohistochemical methods (fluorescent and method with use of peroxidase antiperoxidase complex) with the aid of antiserum serotonin showed the content of serotonin in these cells. Distribution of serotoninergic nerve fibres resemble that of adrenergic fibres with density being significantly lower. The fibres have frequent contacts with mast cells processes. These data indicate the presence of functional connection between serotonin positive nerve fibres and the possibility of their drawings in control of blood circulation of brain.     

Identification of nitric oxide synthases in isolated bovine brain vessels

Initial reports on antiproteinuric effect of pefloxacine in small groups of patients with minimal-change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS) have not been confirmed in other papers. To assess its antiproteinuric effect in experimental animals we administered pefloxacine to rats with adriamycin nephropathy showing morphological changes resembling human minimal-change disease or focal segmental glomerulosclerosis, and clinically with full-blown nephrotic syndrome. Pefloxacine treatment was at least partially effective in preventing further increase of proteinuria in rats with adriamycin nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on the glomerular cytokine network and glomerular production of reactive oxygen species.     

Adrenergic innervation of the cerebral arteries following changes in the activity of cholinergic and monoaminergic brain systems

Bipolar electrical nerve stimulation decreased the adrenergic innervation density and the catecholamine content in the rat isolated caudal artery. Changes in cholinesterase activity and catecholamine content in histochemically active nerves following administration of cholinesterase (AChE) inhibiting agent phosphacol, seem to reflect compensatory responses to increasing dilatory cholinergic vasomotor effects under conditions of the AChE activity. Adrenergic innervation of cerebral arteries was also studied after a 1-hr daily hypoxic sessions. These decreased the catecholamines content as compared to the control.     

Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.     

VIP innervation of the gallbladder

By immunohistochemistry, vasoactive intestinal polypeptide (VIP) was localized to nerve fibres and nerve cell bodies in the gallbladder wall of several mammals, including man. There is thus a morphological basis for accepting the powerful actions of VIP on gallbladder motility as physiological. VIP (vasoactive intestinal polypeptide), first thought of as a gut hormone, has recently been localized to a widely distributed system of nerves in the gut wall 1,2. In addition, nerves displaying VIP immunoreactivity are present in the wall of brain vessels and in the hypothalamus 1,3. Among known effects of VIP are relaxation of the gallbladder and inhibition of CCK-induced gallbladder contraction4,5. These observations prompted a search for VIP in the gallbladder wall. The present report deals with the immunohistochemical demonstration of VIP nerves in the gallbladder of several species, including man.     

Cholinergic receptors in the rat uterus

Natural anti-tumor antibodies (NAA) were revealed, by a complement-dependent cytotoxicity test on el4 lymphoma cells, in the serum of C3Hf but not of C57BL mice. Hybrids between the positive C3Hf and the negative C57Bl mice were NAA producers. Individual variability of NAA level was found in C3Hf and in the hybrids. The study of mice housed in the same or in different cages and of mice belonging to the same or to different litters demonstrated a randomly distributed variability. These observations seem to exclude environmental influences on the natural immune response or genetic mutations in the C3Hf strain with the appearance of variants with different NAA content. The NAA level was age-dependent with a peak around 20-24 weeks of age. Inoculum of lymphoma cells induced an increase in the NAA level both in C3Hf and in the hybrids but not in C57Bl mice which seem therefore incapable of making guinea-pig complement-fixing NAA. The individual variability of NAA level and the stimulating effect of tumor cells support a potential role of NAA in immunosurveillance of oncogenesis.     

Altered response to histamine in brain tumor vessels: the selective increase of regional cerebral blood flow in transplanted rat brain tumor

The authors studied the effect of intracarotid administration of histamine on the regional cerebral blood flow (rCBF) in transplanted rat C6 glioma by the hydrogen clearance method. Histamine infusion at doses of 1 and 10 micrograms/kg/min produced an increase of rCBF in the tumor (24.6% +/- 16.4%, p < 0.002, and 37.6% +/- 18.2%, p < 0.0001, respectively) and also in brain surrounding the tumor (26.8% +/- 16.2%, p < 0.002, and 34.9% +/- 9.2%, p < 0.0001, respectively) without any significant changes in the ipsilateral hemisphere. Intravenous administration of pyrilamine (H1 antagonist) and cimetidine (H2 antagonist) reduced blood flow responses to histamine; cimetidine was a more effective blocking agent than pyrilamine. Intracarotid infusion of histamine (1 and 10 micrograms/kg/min) with intravenous injection of Evans blue dye disclosed the selective extravasation of dye in the tumor and the brain surrounding the tumor. These results indicated that brain tumor vessels could respond to histamine differently than normal brain capillaries. The mechanism of selective response to histamine could be explained either by increased permeability or by altered characteristics of histamine receptors in the tumor vessels.     

Nitrergic innervation of the cat liver

The aim of this work was to study the nitrergic innervation in the liver of the cat using immunocytochemical procedures. At the hepatic hilus, a rich plexus of neuronal nitric oxide synthase immunoreactive (nNOS-IR) nerve fibers and ganglia was detected around the interlobular branch of the bile duct. nNOS-IR nerve fibers were observed running with the components of the intralobular portal triads located close to the hepatic hilus, as well as with a few vessels and ducts of the deeper parenchyma. These latter fibers, beside others located in Glisson's capsule, occasionally showed short ramifications entering the parenchyma itself. The present results suggest that, in the cat liver, nNOS is involved in the autonomic control of hepatic blood flow, with a limited role in the regulation of hepatobiliary excretory activity and hepatocellular metabolic function.     

Peptidergic innervation of the rat cornea

Corneal nerves regulate corneal epithelial integrity, proliferation, and wound healing. The mechanisms by which the nerves mediate their effects remain poorly understood; however, the release of biologically active neuropeptides has been hypothesized. The purpose of the current investigation was to determine the relative densities, distribution patterns, and origins of rat corneal nerves containing each of eight different neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), neuropeptide Y (NPY), methionine-enkephalin (M-ENK), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), and cholecystokinin (CCK). In the first set of experiments, immunohistochemical demonstrations of the above neuropeptides were performed on free-floating corneal sections cut tangential to the corneal surface. The results showed that six of the peptides, CGRP, SP, GAL, NPY, M-ENK, and VIP were present in rat corneal nerves. The innervation patterns of corneal nerves containing each of these six peptides were then documented by mapping all fibers in serial sections from select corneal quadrants onto a series of line drawings by using a drawing tube. In the second set of experiments, the origins of the corneal peptidergic nerve fibers were determined by selective ocular denervations. Unilateral combined sensory and sympathetic ocular denervations or unilateral sympathetic ocular denervations were performed in adult rats by transecting the ophthalmomaxillary nerve and/or removing the superior cervical ganglion. After 5-7 days, each of the ipsilateral corneas was sectioned and processed immunohistochemically for the presence of one of the six peptides found in experiment one, and the fibers that survived the ocular denervations were plotted onto line drawings. Ocular denervations revealed that corneal peptidergic nerves have sensory (CGRP, SP, and GAL), sympathetic (NPY), and parasympathetic (GAL, NPY, M-ENK, and VIP) origins. The results of this investigation have shown that the peptidergic innervation of the rat cornea is more extensive and complex than previously reported. This is the first investigation to show the presence of GAL in the rat cornea, and the first to demonstrate the presence of NPY-, VIP-, and M-ENK-IR nerve fibers in the cornea of any species.     

Small vessels in the human brain: MR venography with deoxyhemoglobin as an intrinsic contrast agent

To assess a magnetic resonance (MR) imaging method for depicting small veins in the brain, a three-dimensional, long echo time, gradient-echo sequence that depended on the paramagnetic property of deoxyhemoglobin was used. Veins with diameters smaller than a pixel were depicted. This MR imaging method is easy to implement and may prove helpful in the evaluation of venous diseases.     

Cholinergic modulation of the content of temporal memory.

The pharmacological effects of anticholinesterases (physostigmine and neostigmine) and cholinergic receptor blockers (atropine and methylatropine) on the content of temporal memory in the rat were studied with the use of a 20-s peak-interval procedure with auditory signals. Physostigmine administered ip decreased the variability of the temporal discrimination and shifted peak times permanently leftward on the time scale in a dose-dependent fashion (0.01, 0.03, & 0.09 mg/kg). Neostigmine (0.03 mg/kg) did not produce any of these effects. Atropine administered ip increased the variability of the temporal discrimination and shifted peak times permanently rightward on the time scale in a dose-dependent fashion (0.05, 0.15, & 0.45 mg/kg). Methylatropine (0.15 mg/kg) did not produce any of these effects. Application of a scalar timing model indicated that physostigmine decreased the remembered times of reinforcement and increased sensitivity to time, whereas atropine increased the remembered times of reinforcement and decreased sensitivity to time. These results suggest that the effective level of brain acetylcholine sets the communication speed for the translation of durations measured by the internal clock into values stored in temporal memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic and adrenergic effects of tityustoxin

The effects of purified scorpion toxin (Tityustoxin or TsTX) were investigated on the isolated guinea-pig and rat ileum, rat spleen strip and hen rectal caecum. The contraction of the ileum was due only in part to the release of acetylcholine, whereas the contraction of the spleen strip and the relaxation of the rectal caecum were due to the release of catecholamines.