Biomedical subjects

S Forsgren

Publications and source records attributed to S Forsgren.

At least 55 records · Page 3Linked to original sources

PubMed1996

Initial increase and subsequent loss of vasoactive intestinal polypeptide immunoreactivity in acetylcholinesterase-positive neurons of mouse islets transplanted to the kidney.

Collagenase-isolated pancreatic islets from C57BL/6J mice were cultured overnight and transplanted under the kidney capsule of non-diabetic syngeneic hosts. Cryostat sections of grafts and fresh islets were stained for acetylcholinesterase (AChE) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI). Immediately after isolation, as well as 2-5 days after transplantation, VIP-LI- and AChE-positive nerve cell bodies were clearly seen in the periphery of the islets. Grafts 3-5 days old exhibited a transient and marked increase in VIP-LI nerve cell bodies and fibres. Seven days after transplantation VIP-LI nerve structures began to decrease in number and after 26-52 weeks they were no longer detectable. In contrast, AChE-positive nerve cell bodies and fibers, which showed a relatively constant pattern of distribution, were observed throughout the entire observation period. Restaining experiments demonstrated the coexistence of VIP-LI and AChE activity in the neurons. It is concluded that the grafts were extensively equipped with an intrinsic VIP-ergic and AChE-positive innervation. The initial, transient enhancement of VIP-LI expression probably reflects an adaptation of the neuro-insular complex to the preganglionic denervation, or to the ectopic environment, or both.

Acetylcholinesterase↗

PubMed1996

Similar distribution of mast cells and substance P- and calcitonin gene-related peptide-immunoreactive nerve fibers in the adult human larynx.

The mechanisms causing supraglottic and subglottic edema in the human larynx are not fully understood. Substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing nerve fibers and mast cells have been suggested to induce inflammation and edema in other parts of the body. In this study of the adult human larynx the distribution of mast cells was studied in relation to SP- and CGRP-containing nerve fibers. Substance P- and CGRP-immunoreactive nerve fibers and numerous mast cells were found in the epiglottis and in the subglottic region of the larynx. Only occasional mast cells and no nerve fibers showing SP- or CGRP-like immunoreactivity were found in the vocal cords. In conclusion, the present study has shown that the distribution of nerve fibers showing SP- and CGRP-like immunoreactivity and mast cells has a similar regional variability. As the highest density of SP- and CGRP-containing nerve fibers and mast cells was present in the regions of the larynx where edema occurs, SP, CGRP, and/or mast cells might be involved in the pathogenesis of edema.

Adult↗

PubMed1996

Mast cells in the laryngeal mucosa of the rat. Effect of compound 48/80 and dexamethasone: a quantitative and immunohistochemical study at the light- and electron-microscopic levels.

Mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) in the epiglottic and subglottic regions in the rat larynx were characterized and quantified by immunohistochemistry and by light and electron microscopy, in control rats and rats injected intraperitoneally with dexamethasone and compound 48/80. Considerable regional differences were observed in the distribution of mast cells, especially in the epiglottis, where most cells were located on the laryngeal side. In the epithelium of the subglottic region the MMCs showed immunoreactivity for 5-hydroxytryptamine, in contrast to the epithelial MMCs in the epiglottis. In ultrathin sections, the subglottic MMCs contained larger but fewer granules compared with the epiglottic MMCs. After treatment with dexamethasone, the MMCs in the epithelium disappeared, while after treatment with compound 48/80 a large number of the CTMCs in the lamina propria became degranulated, though still present. This study shows that MMCs in the epiglottic and subglottic regions may be of two subtypes, differing in number and size of the granules as well as in chemical content.

Animals↗

PubMed1995

Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation.

PURPOSE: The expression of different neuropeptides in the innervation of submandibular and parotid glands of the rats was examined 2 and 5 days after initiation of radiation treatment as well as 10 and 180 days following the termination of irradiation. METHODS AND MATERIALS: The irradiation was given on 2 or 5 consecutive days with daily doses of 4-8 Gy up to a total dose of 20-40 Gy. Immunohistochemical methods were used for the demonstration of substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and, the rate-limiting enzyme in the catecholamine synthetic pathway, tyrosine hydroxylase (TH). The content of SP was also analyzed by the use of radioimmunoassay (RIA). RESULTS: In the parenchyma of both the submandibular and the parotid glands of control animals as well as after 2 days of irradiation treatment, a few nerve fibers showing SP-like immunoreactivity (LI) were observed. A marked increase in the expression of SP in the innervation of the parenchyma in both glands was observed 10 days after cessation of radiation treatment. The number of stained nerve fibers and the intensity of fluorescence in the fibers seemed to be dose dependent because the group subjected to a total dose of 40 Gy displayed a more pronounced staining intensity than that treated with 30 Gy. These results were supported by the RIA analysis. One hundred eighty days after treatment no obvious differences in SP-expression were seen between control and irradiated animals. No acute and long-term alterations were seen with regard to the other peptides and TH. CONCLUSIONS: These results suggest that specific dose- and time-dependent changes in the expression of SP in the parenchyma of both submandibular and parotid glands occur in response to fractionated irradiation. The observations add further aspects to the tissue differences in physiological response and sensitivity to irradiation.

Animals↗

PubMed1995

Bombesin-like immunoreactivity in the rat larynx: increase in response to irradiation.

It is previously well known that bombesin has effects as growth factor and that changes in bombesin content in air-way structures occur in various patho-physiological conditions. In the present study, the effects of radiotherapy on bombesin expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 gray daily. Ten days after cessation of irradiation, the subglottic part of the larynx from irradiated and control animals was dissected out, and processed for immunohistochemistry or radioimmunoassay. The radioimmunoassay analysis showed that the content of bombesin-like material increased 2-fold after irradiation. The immunohistochemical analysis displayed an increased bombesin-like immunoreactivity in local ganglionic cells and in nerve fibers in the submucosal glands. These nerve fibers are likely to be derived from the local ganglionic cells. On the other hand, there was no change in the pattern of immuno-reactivity in the innervation of the epithelium and the lamina propria, including the blood vessels. The observations show that radiotherapy can be added to the list of factors that influence bombesin expression in airway structures.

Animals↗

PubMed1995

Irradiation influences the expression of substance P and enkephalin in the rat larynx.

The effects of radiotherapy on neuropeptide expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 Gray daily. Ten days after the end of irradiation, the larynx, the laryngeal nerves and different ganglia related to the larynx were dissected out from irradiated and control animals and processed for neuropeptide immunohistochemistry. There was an increased immunolabelling for two of the neuropeptides tested, substance P and enkephalin, in the innervation of the subglottic glands and in the acetylcholinesterase-positive ganglionic cells of the local ganglia. These cells were interpreted as representing postganglionic parasympathetic ganglionic cells. The changes seen in the subglottic glands were interpreted as most likely being related to the changing pattern of staining seen in the local ganglia. No changes in substance P- and enkephalin expression were observed in other laryngeal structures, the nodose ganglia, superior cervical ganglia or laryngeal nerve paraganglia. Thus, in certain respects neuropeptide expression in the larynx is modulated by radiotherapy. Since neuropeptides have both neurotransmitter and/or neuromodulator effects in airway tissue and since they show effects as growth factors, the occurrence of this plasticity in neuropeptide expression should be taken into consideration in future studies examining the effects of irradiation on normal/diseased airway tissues.

Animals↗

PubMed1995

Expression of neuropeptides (CGRP, substance P) during and after orthodontic tooth movement in the rat.

The present study was designed to investigate the changes in patterns of calcitonin gene-related peptide (CGRP) and substance P (SP) innervation during buccally-directed orthodontic tooth movement (OTM) of the first maxillary molar in the rat. In addition, the CGRP- and SP-innervation was examined 14 and 28 days after the orthodontic force was discontinued. Comparisons were made with the innervation found in control animals. Orthodontic appliances produced a buccally directed force in the range of 20-50 g on the upper right first molar for either 24 hours or 3 days. When the orthodontic appliances were removed one group of animals were killed immediately, whereas the other groups were killed after a healing period of 14 days or 28 days. After fixation the upper jaws were decalcified, frozen, and sectioned in the frontal plane at the level of the first and second molars. The sections were processed for CGRP, SP, and routine morphology. An increase was found in the number of nerve fibres showing CGRP-like immunoreactivity (LI) in the pulp, periodontal ligament (PDL) and marginal gingivae with the fibres showing a higher intensity of immunolabelling after 24 hours or 3 days of OTM. The contralateral first upper molar showed an increase in the expression of CGRP. Fourteen days after removal of the appliances, there was still a marked CGRP-innervation of the PDL in test teeth as well as in contralateral teeth. After 28 days, a decrease in CGRP-innervation was observed, but this innervation was still more pronounced than that found in the controls. The pattern of SP-innervation changed similarly to that of the CGRP-innervation, however, the nerve fibres showing SP-LI were considerably fewer than those showing CGRP-LI at all stages and in all areas. This study suggests that CGRP- and SP-changes not only occur in the tooth exposed to buccally directed OTM, but also in the contralateral tooth and that the changes are evident for a considerable time after terminating OTM.

Animals↗

PubMed1995

Anatomic relationship between substance P- and CGRP-immunoreactive nerve fibers and mast cells in the palatal mucosa of the rat.

The study describes the distribution of mast cells and of substance P (SP) and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the rat palatal mucosa, focusing on the anatomic relationship between these tissue elements. The maxilla of 10-14-wk-old rats was dissected free, fixed, demineralized and frozen. Consecutive sections were stained with avidin peroxidase or processed for immunohistochemistry. In order to define the correlation between nerve fibers and mast cells, double staining techniques were used. The distance between each avidin-positive mast cell and the nearest detectable nerve fiber was determined. 5-Hydroxytryptamine- (5-HT) and avidin peroxidase-positive mast cells were frequently seen in the palatal mucosa but were rarely found in the gingival area. A large number of nerve fibers showing SP- and CGRP-like immunoreactivity were seen, particularly in association with blood vessels. Some nerve fibers were located in contact with or very close to the mast cells but the vast majority of mast cells showed no close anatomic association to nerve fibers. The nerve fibers and mast cells were mainly concentrated to the same regions in the palatal mucosa where blood vessels occurred. The observations suggest that in the rat palatal mucosa the main functional relationship relates to SP/CGRP and the blood vessels, and only to a minor degree to SP/CGRP and mast cells.

Animals↗

PubMed1995

Immunoreactive atrial and brain natriuretic peptides are co-localized in Purkinje fibres but not in the innervation of the bovine heart conduction system.

Recently, we observed that atrial natriuretic peptide (ANP) immunoreactivity was present in Purkinje fibres and nerve fibre varicosities in the conduction system of the bovine heart. In order to elucidate further the morphological correlation between natriuretic peptides and the conduction system, the distribution of brain natriuretic peptide (BNP) was examined. The different parts of the conduction system in the bovine heart were dissected out and processed for immunohistochemistry with antisera against BNP and ANP. BNP immunoreactivity was frequently observed in Purkinje fibres of the atrioventricular bundle, whereas only a few Purkinje fibres in the ventricular part of the conduction system showed immunoreaction. BNP immunoreactivity was detected in regions of the Purkinje fibres which also showed ANP immunoreactivity. BNP immunoreactivity was not observed in nerve fibre varicosities. Methodologically, a larger number of small BNP immunofluorescent granular structures was observed by using an elution-restaining technique instead of conventional immunohistochemistry. The present study shows that BNP and ANP immunoreactivities frequently occur in the atrioventricular bundle and that they are co-localized in Purkinje fibres, but not in nerve fibre varicosities, in the conduction system. As previously has been proposed for ANP, the present observations suggest that also BNP may act in an autocrine and/or paracrine way in the conduction cells.

Animals↗

PubMed1994

Atrial natriuretic peptide in the innervation of the bovine heart conduction system: relationship with substance P and autonomic innervation--immunohistochemical studies.

Recently, we observed that atrial natriuretic peptide (ANP) immunoreactivity (IR) was present not only in the Purkinje fibres, but also in nerve fibre varicosities in the conduction system of the bovine heart. These findings and previous observations that ANP is able to influence autonomic neurotransmission in the heart, lead us to elucidate the possible occurrence of ANP in the sympathetic and/or parasympathetic nervous systems and/or in various types of peptidergic innervation in the conduction system. The different parts of the conduction system of bovine hearts were dissected out and processed for immunohistochemistry including double-staining, using antisera against ANP, tyrosine hydroxylase and different neuropeptides. We observed that some of the nerve fibre varicosities exhibiting ANP-IR showed substance P-IR and that ANP was present as scattered immunoreactive granules in intracardial, presumably parasympathetic, ganglionic cells. The study shows that ANP is likely to be present in parasympathetic innervation and in afferent nerve endings in the bovine heart conduction system.

Animals↗

PubMed1994

Innervation of laryngeal nerve paraganglia: an anterograde tracing and immunohistochemical study in the rat.

Carotid body-like organs, paraganglia, frequently occur in the superior and recurrent laryngeal nerves. The paraganglia are supplied with a rich innervation of unknown origin. In the present study, the origin of the innervation of the paraganglia of the rat was studied with two different techniques. One approach was anterograde tracing of wheat-germ agglutinin-horseradish peroxidase after injection into the nodose and jugular ganglia of the vagus and the superior cervical ganglion. The other approach was immunohistochemical staining for neuropeptides after excision of the superior cervical ganglion, or vagotomy. Antisera against neuropeptide Y, vasoactive intestinal polypeptide, and calcitonin gene-related peptide were utilized. Both the tracing method and calcitonin gene-related peptide immunohistochemistry after vagotomy showed that the paraganglia receive sensory innervation from the vagal ganglia. No labeling was detected in the paraganglia after injection of wheat-germ agglutinin-horseradish peroxidase in the superior cervical ganglion. Excision of this ganglion did not lead to a decrease in the neuropeptide-Y innervation in the paraganglia, but most of this innervation in the surrounding blood vessels disappeared. The observations show that the superior cervical ganglion does not contribute to the innervation in the paraganglia and that the neuropeptide-Y innervation of the blood vessels originates from the superior cervical ganglion whereas that of the paraganglia has another origin, most likely local ganglionic cells. The results also suggest that the vasoactive intestinal polypeptide innervation in the paraganglia arises from local ganglionic cells. The two approaches complemented each other in mapping the afferent and efferent nerve supply of the paraganglia.

Animals↗

PubMed1994

Distribution of calcitonin gene-related peptide-like immunoreactivity in the bovine conduction system: correlation with substance P.

The role of calcitonin gene-related peptide (CGRP) in the heart conduction system is unclear. In the present study, the distribution of CGRP in relation to that of substance P (SP) was examined in the bovine conduction system using immunohistochemical methods. Varicose nerve fibres showing CGRP-like immunoreactivity (LI) were frequently observed in the nerve fascicles, some of these fibres often also showing SP-LI. A few fibres exhibiting CGRP-LI were also observed in the intrinsic ganglia. In blood vessel walls and particularly in the conduction tissue, i.e., in association with the nodal cells and the Purkinje fibres, there were only a few varicose fibres showing both CGRP- and SP-LI, whilst there was a large number of varicose fibres showing only SP-LI. The observations show that the main morphologic correlate for the occurrence of CGRP-effects in the bovine conduction system is varicose nerve fibres located in the nerve fascicles. The observations also suggest that CGRP has effects at the intrinsic ganglia and that SP predominates over CGRP in the innervation of blood vessel walls and the conduction tissue.

Animals↗

PubMed1994

Effects of irradiation on neuropeptide expression in rat salivary gland and spinal cord.

It is well-known that a large number of factors can influence the expression of neuropeptides in the nervous system. In the present study, the effects of unilateral and bilateral irradiation to the rat head and neck on the expression of neuropeptides in the innervation of the submandibular gland and in the ganglionic cells of the submandibular ganglion was examined ten days and six months after treatment. Antisera directed against enkephalin and bombesin and immunohistochemical methods were used. The effects of bilateral irradiation on the staining pattern of various neuropeptides in the cervical spinal cord were also studied. In the submandibular gland and in the submandibular ganglionic cells, there was a markedly increased neuropeptide expression ten days after bilateral treatment, as seen after staining with both antisera used, while no changes occurred after unilateral treatment. Six months after treatment, the pattern of neuropeptide expression in the submandibular gland/ganglion corresponded to that seen in controls. Irradiation did not lead to any changes in the staining pattern of neuropeptides in the spinal cord. The observations show that there is a great complexity in the susceptibility of nervous tissues to radiotherapy with respect to influences on the expression of neuropeptides.

Animals↗

PubMed1993

Presence of immunoreactive atrial natriuretic peptide in nerve fibres and conduction cells in the conduction system of the bovine heart.

Previous findings of atrial (A-type) natriuretic peptide (ANP) in nervous tissue, such as the brain and the superior cervical ganglia, led us to investigate the possible occurrence of ANP in nervous tissue in the heart. The distribution of ANP in the bovine heart, particularly its conduction system, was examined by the use of immunohistochemical methods and an antiserum against alpha-hANP. ANP immunoreactivity was frequently detected in atrial myocytes and in the Purkinje fibres of the AV-bundle, and was sometimes seen in the Purkinje fibres of the bundle branches and their ramifications. On the other hand, ANP immunoreactivity was never seen in the conduction cells of SA- and AV-nodes. ANP immunoreactivity was also detected in small nerve-fibre varicosities, mainly in the AV-node and AV-bundle. Most of these varicosities were located in the proximity of the conduction cells, but some occurred close to fine blood vessels or in the walls of arterioles. These observations show for the first time that ANP immunoreactivity is present not only in atrial myocytes and conduction cells but also in nerve-fibre varicosities in the conduction system. The observations suggest that ANP may act as a neuromodulator and/or neurotransmitter in the conduction system.

Animals↗

PubMed1993

Calcitonin gene-related peptide expression at endplates of different fibre types in muscles in rat hind limbs.

Calcitonin gene-related peptide (CGRP) occurs only in some motoneurons. In this study, the presence of CGRP in motor endplates in relation to muscle fibre types was examined in slow (soleus muscle) and fast [tibialis anterior (TA) and extensor digitorum longus (EDL)] leg muscles of the rat. CGRP was detected by use of immunohistochemical methods, and staining for the mitochondrial-bound enzyme NADH-TR was used for demonstration of fibre types. The fibres showing low NADH-TR activity were interpreted as representing IIB fibres. All such fibres located in the superficial portion of TA were innervated by endplates displaying CGRP-like immunoreactivity (LI), whereas in the deep portion of TA some of these fibres lacked CGRP-LI at their endplates. Thirty per cent of the IIB fibres in EDL showed CGRP-LI at the endplates. All fibres in TA and EDL displaying high NADH-TR activity and interpreted as type-IIA fibres, lacked CGRP-LI in their motor innervation. One third of the fibres with intermediate NADH-TR activity in TA exhibited CGRP-LI at their endplates, whereas in EDL only few such fibres displayed CGRP-LI in the endplate formation. These fibres are likely to belong to type-IIX or type-I motor units. CGRP-LI was very rarely detected at the endplates in the soleus muscle. These observations show that distinct differences exist between the slow muscle, soleus, and the fast muscles, TA and EDL, but that there are also differences between the different types of fibres in TA and EDL with respect to presence of CGRP-LI at the endplates.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1993

Irradiation-induced effects on the innervation of rat salivary glands: changes in enkephalin- and bombesin-like immunoreactivity in ganglionic cells and intraglandular nerve fibers.

When treating head and neck for cancer with the use of radiotherapy the salivary glands are usually within the treatment volume with ensuing dryness and discomfort. Since the autonomic nervous system is of pivotal importance for the salivary gland function and integrity, the irradiation-induced effects may involve an influence on the innervation of salivary glands. Therefore, the rat submandibular gland, including the submandibular ganglionic cells, has been subjected to immunohistochemical examination with respect to expression of neuropeptides following fractionated irradiation with high energy photons. A markedly enhanced expression of bombesin- and leu-enkephalin-(ENK)-like immunoreactivities (LI) in the ganglionic cells and a pronounced increase in the number of nerve fibers showing these immunoreactivities in the submandibular gland tissue following irradiation were observed 10 days after treatment. On the other hand, no changes in the patterns of VIP (vasoactive intestinal polypeptide)- and NPY (neuropeptide Y)-immunoreactivities occurred. Thus, the present study shows that alterations in the expression of certain neuropeptides take place in the submandibular gland and its associated ganglionic cells in response to irradiation of the head and neck region. These changes may add further explanation to the inherent radiosensitivity of salivary glands.

Animals↗

PubMed1992

Studies on the distribution of calcitonin gene-related peptide-like and substance P-like immunoreactivities in rat hind limb muscles.

The tibialis anterior, extensor digitorum longus and soleus muscles in the rat were examined with respect to the presence of calcitonin gene-related peptide-like as well as substance P-like immunoreactivity. In some of the motor endplates in these muscles, identified by staining for acetylcholinesterase activity, calcitonin gene-related peptide-like immunoreactivity was detected, but in others it was not. Calcitonin gene-related peptide-like immunoreactivity was found to coexist with substance-P-like immunoreactivity in nerve fibres located outside and inside the capsule of the muscle spindles, as well as in nerve fibres located in nerve fascicles. These fibres presumably represent sensory nerve fibres. Calcitonin gene-related peptide-like immunoreactivity, but not substance P-like immunoreactivity, was also detected in cap-like structures located on the surface of the intrafusal muscle fibres in the polar regions of the spindles, structures which are likely to correspond to motor plate endings. The observations suggest that calcitonin gene-related peptide is heterogeneously present in the endplates of rat hind limb muscles, and gives for the first time immunohistochemical evidence for the presence of calcitonin gene-related peptide and substance P in the innervation of muscle spindles.

Animals↗

PubMed1992

Expression of catecholamine-synthesizing enzymes in paraganglionic and ganglionic cells in the laryngeal nerves of the rat.

The rat recurrent and superior laryngeal nerves with adjacent connective tissue were examined by immunohistochemical techniques for localization of the catecholamine-synthesizing enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase. Most of the cells in the paraganglia of the recurrent and superior laryngeal nerves showed an intense tyrosine hydroxylase-like immunoreactivity. A few paraganglionic cells exhibited dopamine-beta-hydroxylase-like immunoreactivity while none of the cells displayed phenylethanolamine-N-methyltransferase-like immunoreactivity. Some of the ganglionic cells in the recurrent and superior laryngeal nerves showed dopamine-beta-hydroxylase-like immunoreactivity whilst these cells never showed tyrosine hydroxylase- or phenylethanolamine-N-methyltransferase-like immunoreactivity. The arterioles were supplied with plexuses of nerve fibres showing tyrosine hydroxylase- and dopamine-beta-hydroxylase-like immunoreactivity. The results indicate that dopamine is the major catecholamine located in the laryngeal nerve paraganglia and show that ganglionic cells in the recurrent and superior laryngeal nerves show immunolabelling for one of the enzymes in the catecholamine synthetic pathway, dopamine-beta-hydroxylase.

Animals↗