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Biomedical subjects

T Cowen

Publications and source records attributed to T Cowen.

At least 73 records · Page 4Linked to original sources

A quantitative study of changes in old age of 5-hydroxytryptamine-like immunoreactivity in perivascular nerves of the rabbit.

Quantitative immunohistochemical techniques were applied to whole mount stretch preparations of the femoral, saphenous and cerebral blood vessels of rabbits from before birth to old age (greater than 3 years) in order to study the effects of ageing processes on 5-hydroxytryptamine(5-HT)-like immunoreactive perivascular nerve plexuses. Immunostained perivascular nerve fibres first appeared at 30 days in utero in all the vessels studied with the exception of the saphenous vein where nerves appeared at one day after birth. Perinatal and early postnatal development showed a general increase in nerve density in all the vessels, which continued up to adulthood (6 months) in all vessels except the femoral artery and then showed a general and often statistically significant decline in old age. Comparison of these results with those of noradrenergic perivascular innervation showed by 5-HT tended to appear later in perinatal development and was more widely reduced in old age than noradrenaline.

Aging↗

Effect of oestrogen and progesterone on noradrenergic nerves and on nerves showing serotonin-like immunoreactivity in the basilar artery of the rabbit.

The effects of oestrogen and progesterone on noradrenergic nerves and nerves with serotonin (5-HT)-like immunoreactivity in the basilar artery were investigated in the rabbit using whole-mount stretch preparations. The noradrenergic nerves were demonstrated by glyoxylic acid fluorescence histochemistry and nerves with 5-HT-like immunoreactivity by indirect immunofluorescence techniques. Quantitative image analysis of fluorescent nerve fibres revealed that nerve density and varicosity diameter of nerves with 5-HT-like immunoreactivity were significantly (P less than 0.01 and P less than 0.05 respectively) reduced after 4-week administration of oestrogen and the intensity of fluorescence was also reduced. However, there were no significant changes after progesterone. Neither oestrogen nor progesterone had any effect on noradrenergic innervation. The findings are discussed in relation to higher incidence of migraine headaches in females taking oral contraceptives.

Adrenergic Fibers↗

Increase in neuropeptide Y, but not noradrenaline, in the superior cervical ganglion of rabbits chronically exposed to cold.

We have investigated the effects of exposure to cold for 8 days on sympathetic neurones supplying the ear artery of the rabbit using a combination of assay and quantitative morphological techniques. The concentration of neuropeptide Y was shown to be significantly higher in the superior cervical ganglion of cold-exposed animals. Although the noradrenaline and dopamine levels in the ganglion were not significantly changed, the ratio of noradrenaline to dopamine was significantly increased after exposure to cold. The density of noradrenergic nerves supplying the ear artery was found to be unaffected by cold exposure. Since noradrenaline and neuropeptide Y have been shown to coexist in the majority of neurones of the superior cervical ganglion, the present study appears to provide an example of differential control of expression of neurotransmitters contained within the same neurone.

Animals↗

The origin and distribution of 5-hydroxytryptamine-like immunoreactive nerve fibres to major mesenteric blood vessels of the rat.

5-Hydroxytryptamine-like immunoreactive nerve plexuses were demonstrated by indirect immunofluorescence histochemistry in whole-mount preparations and cryostat sections of blood vessels from the mesenteric vasculature of the adult rat. The major veins showed a density of innervation greater than that of the accompanying arteries. Removal of the coeliac-superior mesenteric ganglion complex resulted in almost total loss of 5-hydroxytryptamine-like immunoreactive nerves from superior mesenteric blood vessels. The results of crush lesions applied to distal vessels of the superior mesentery indicate that there were no 5-hydroxytryptamine-like immunoreactive nerve fibres extending from the enteric nervous system to these vessels. The administration of 6-hydroxydopamine resulted in a large reduction in the noradrenergic innervation, accompanied by a similar fall in the number of 5-hydroxytryptamine-like immunoreactive nerve fibres. It is suggested that the cell bodies of the 5-hydroxytryptamine-like immunoreactive nerve fibres demonstrated in the superior mesenteric vasculature are located within the sympathetic ganglia which supply the noradrenergic innervation to the same region and that the 5-hydroxytryptamine-like immunoreactivity may be co-localized with noradrenaline within sympathetic nerve fibres.

Animals↗

Origin and postnatal development of nerves showing 5-hydroxytryptamine-like immunoreactivity supplying major cerebral arteries of the rat.

Nerve plexuses showing 5-hydroxytryptamine (5-HT)-like immunoreactivity (5-HTLI) have been demonstrated in all the major cerebral arteries of the rat using fluorescence immunohistochemistry on whole-mount stretch preparations. Following bilateral superior cervical ganglionectomy, nerves disappeared from all the vessels studied with the exception of the vertebral and basilar arteries where fibres remained. Using image analysis, the density of nerves containing 5-HTLI showed little change between vessels from 3 to 4-week-old and 6 to 7-week-old animals, in contrast to another study which has shown marked reductions in 5-HT-immunoreactive neuronal cell bodies in the superior cervical ganglion over the same period of early development. It was concluded that while the terminals of cerebrovascular nerves retain the capacity to synthesise and/or store 5-HT throughout life, their cell bodies may lose this function soon after birth.

Animals↗

Pre- and postnatal development of adipose tissue at four sites in the guinea pig: effect of maternal diet restriction during the second half of pregnancy.

The effect of maternal diet restriction on the subsequent development of four adipose tissue depots has been studied in the guinea pig. Fetuses taken from, and pups born to, pregnant sows fed ad libitum (AL) displayed an increase in fat pad mass and in fat cell mass with increasing body mass at the four selected depots (interscapular (IS), retroperitoneal (RP), groin side subcutaneous (GS) and behind arm subcutaneous (BA)). The effect of maternal diet restriction (50% AL rations during the second half of pregnancy) was to significantly reduce the body masses at birth of the pups. The masses of the BA and GS fat pads and the mass of fat cells in the depots were reduced accordingly. However, the fat depot masses and fat cell masses of the IS and RP fat pads were larger than those of pups of comparable body mass born to AL fed sows. Diet restriction during the second half of pregnancy exerted preferential 'sparing' effects on the 'thermogenic' adipose tissue depots (IS and RP) suggesting the possibility that 'thermogenic' adipose tissue is more likely to be 'programmed' earlier in pregnancy than 'storage adipose tissue' (BA and GS).

Adipose Tissue↗

5-HT-containing nerves to major cerebral arteries of the gerbil originate in the superior cervical ganglia.

This study has shown that over 95% of the 5-hydroxytryptamine (5-HT)-containing nerves to major cerebral arteries in the gerbil share a common origin with noradrenergic cerebrovascular nerves in the superior cervical ganglia. A small group of 5-HT-containing and noradrenergic nerves to the vessels of the posterior brain circulation had a different origin, which may be either central or peripheral. The pial blood vessels of the gerbil appeared to have no 5-HT-containing nerve supply. The effects of unilateral superior cervical ganglionectomy on 5-HT-containing and noradrenergic nerves to the arteries of the circle of Willis were different. Our results showed total loss of 5-HT-containing nerves on the vessels ipsilateral to the ganglionectomy combined with ca. 50% reductions of nerve density on the vessels of the contralateral side. There were no contralateral reductions of noradrenergic nerve density in parallel experiments although again the ipsilateral side was totally denervated. We suggest that 5-HT-containing cerebrovascular nerves are differently distributed as well as being in some way more sensitive to nerve damage compared to noradrenergic cerebrovascular nerves. The relationship between a combined serotonergic and noradrenergic vasoconstrictor control of large cerebral blood vessels and serotonergic vasodilation of small pial blood vessels is discussed.

Afferent Pathways↗

Perivascular noradrenergic and peptide-containing nerves show different patterns of changes during development and ageing in the guinea-pig.

The development of noradrenergic and peptide-containing perivascular nerves in common carotid, mesenteric, renal and femoral arteries of the guinea-pig was studied using the glyoxylic acid fluorescence and indirect immunofluorescence techniques on whole-mount stretch preparations at 6 stages between 6 weeks in utero and two years after birth. The noradrenergic plexus was more dense than the peptide-containing nerve plexuses in all the blood vessels, and, in general, calcitonin gene-related peptide-containing nerves were more numerous than substance P-containing nerves which in turn were more numerous than vasoactive intestinal polypeptide-containing nerves. In mesenteric and carotid arteries, noradrenergic nerve density reached a peak at about 4 weeks after birth that was maintained to old age, whereas the peptide-containing vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) nerve plexuses reached a peak at birth and declined thereafter to about half maximum density in old age. In contrast, in the renal and femoral arteries, peptide-containing nerves reached a maximum density at 4 weeks after birth, while noradrenergic nerve density reached a peak around birth; both noradrenergic and peptide-containing nerve plexuses declined in density in old age. Of the 4 vessels studied, the mesenteric artery showed the greatest density of innervation for both noradrenergic and peptide-containing nerves at all stages of development, while the femoral artery was the least innervated. The possibility that some perivascular peptide-containing nerves play a trophic role during development is discussed.

Aging↗

Cerebral perivascular serotonergic fibres have a peripheral origin in the gerbil.

The origin of serotonergic nerves supplying the large cerebral vessels of the gerbil has been investigated after bilateral superior cervical ganglionectomy. Immunohistochemical techniques were applied to whole-mount stretch preparations of the cerebral vessels. Removal of both ganglia resulted in the complete loss of immunoreactive fibres in the vessels supplied by the internal carotid artery and in a marked reduction of fibres innervating vessels of the vertebro-basilar system, indicating that most of the cerebrovascular serotonergic nerves have a peripheral sympathetic origin in the gerbil. The contrast with the central origin of serotonergic perivascular nerves claimed in the rat is discussed.

Animals↗

Perivascular nerve types supplying cerebral blood vessels of the gerbil.

The present study shows that cerebral blood vessels of the gerbil resemble other species in being richly supplied by NA-, 5-HT- and NPY-containing nerves. By contrast, the peptidergic nerves containing SP, CGRP and VIP are less dense. The results of superior cervical ganglionectomy show that the SCG is the principal source of NA-, NPY- and 5-HT containing cerebrovascular nerve fibres in the gerbil. The substances seem likely to coexist in some perivascular nerve fibres.

Animals↗

Pontamine sky blue: a counterstain for background autofluorescence in fluorescence and immunofluorescence histochemistry.

The stain pontamine sky blue (PSB) has been shown to reduce background autofluorescence in catecholamine fluorescence and immunofluorescence histochemical preparations. Using PSB as a counterstain on whole-mount stretch preparations of human mesenteric blood vessels, a medium dense noradrenergic nerve plexus is clearly revealed, which previously had been only partially visible because of background autofluorescence. Image analysis of nerve densities in whole-mount stretch preparations of guinea-pig arteries containing noradrenergic, substance P-, and vasoactive intestinal polypeptide (VIP)-positive nerve plexuses shows that PSB staining does not alter the specific neuronal fluorescence and that it improves image definition.

Animals↗

The nerves to blood vessels supplying blood to nerves: the innervation of vasa nervorum.

Noradrenergic, serotoninergic and peptidergic nerves have been demonstrated in perivascular plexuses of vasa nervorum of sympathetic, parasympathetic and somatic nerve trunks. 5-Hydroxytryptamine-, vasoactive intestinal polypeptide- and substance P-containing fibers were found by immunohistochemistry to variable extents in whole mounts of the epineurium of sciatic, vagus and paravertebral sympathetic chains of rabbits. Innervation increased with age. This suggests an hitherto unsuspected role for these vasoactive substances in normal blood flow to nerves and in the genesis of experimental and human neuropathies.

Age Factors↗

Image analysis of FITC-immunofluorescence histochemistry in perivascular substance P-positive nerves.

The ability of image analysis to quantify nerves labelled by FITC-immunofluorescence histochemistry has been tested on whole-mount stretch preparations of perivascular substance P-positive nerves. It has been shown that image analysis can make consistent measurements of nerves demonstrated by immunohistochemistry despite the fading of FITC-fluorescence which occurs during storage and on exposure to ultraviolet light.

Animals↗

An ultrastructural comparison of neuromuscular relationships in blood vessels with functional and 'non-functional' neuromuscular transmission.

The neuromuscular relationships of the guinea-pig renal artery, which has previously been shown to be noradrenergically innervated but 'non-functional', i.e. not responsive to nerve stimulation in vitro, is compared with those of two arteries where functional neuromuscular transmission occurs: the carotid artery, where responses to nerve stimulation are slow and of medium amplitude, and the mesenteric artery, where the responses to nerve stimulation are relatively fast and of large amplitude. Substantial differences of ultrastructure were demonstrated. In the renal artery, there were no nerve varicosities closer than 400 nm to the smooth muscle layer, all varicosities had connective tissue interposed between them and the muscle wall, and there were significantly fewer varicosities (6 +/- 3.1 mm-1) compared with the carotid (33 +/- 8.3 mm-1; P less than 0.05) or mesenteric (105 +/- 15.8 mm-1; P less than 0.001) arteries. In the carotid artery, a small group of varicosities (17%), with little interposed connective tissue, had an average neuromuscular gap of 1.5 micron, whilst the remainder were separated by an average of 4.3 micron and by cellular and other connective tissue elements from the nearest smooth muscle cell. In the mesenteric artery, about half of the nerve varicosities were closer than 400 nm to the muscle layer and 25% of the varicosities had no connective tissue except basal lamina interposed in the neuromuscular space. Differences were also shown in the ultrastructural appearance of the nerves: analysis of the neuronal vesicles showed that the majority of varicosities were noradrenergic in all three vessels, with non-adrenergic varicosities forming 6% of the total in the carotid artery and 32% of the total in the mesenteric artery. Noradrenaline content was greater in the mesenteric artery (0.37 +/- 0.052 ng mm-2) compared with the carotid (0.17 +/- 0.017 ng mm-2; P less than 0.01) and renal (0.11 +/- 0.024 ng mm-2; P less than 0.01) arteries. These differences appear to correlate with the differences of neuromuscular activity in the three arteries.

Animals↗

Reduction in noradrenergic perivascular nerve density in the left and right cerebral arteries of old rabbits.

With the use of fluorescence and acetylcholinesterase histochemistry, marked reductions have been shown in the noradrenergic and acetylcholinesterase-positive innervation of the right ( RMC ) and left (LMC) middle cerebral arteries of old compared with young adult rabbits. The decrease in noradrenergic nerve density tended to be greater in LMC than in RMC : Nerve density fell by approximately 45% in LMC and by approximately 30% in RMC . The reductions in acetylcholinesterase-positive nerves were similar in both LMC and RMC (29 and 33%, respectively). Vessel circumference and cross-sectional wall area appeared to increase in old age in LMC and RMC .

Acetylcholinesterase↗

Development and ageing of perivascular adrenergic nerves in the rabbit. A quantitative fluorescence histochemical study using image analysis.

Age-related changes in vascular adrenergic nerves of 5 contrasting arteries in the rabbit were studied from before birth through to old age. Adrenergic nerves were demonstrated on stretch preparations using glyoxylic acid fluorescence histochemistry. Quantitative estimates of the densities of nerve fibres and varicosities were obtained by automated light microscopic image analysis. The early stages of development of vascular innervation were similar in all the vessels studied. They consisted of a period of outgrowth of axons; a period of rapid increase in density and formation of varicosities; and a later period of more gradual nerve growth. The timing of these stages varied greatly between the different vessels. The larger vessels, i.e. the carotid, renal and femoral arteries, had a well-developed innervation at birth, whilst the innervation of the smaller mesenteric and basilar arteries was sparse. Nerve loss occurred between 6 weeks and 6 months in the femoral artery and in old age (3 years or over) in the renal and carotid arteries. The large elastic arteries were, in general, more densely innervated than the smaller muscular arteries throughout life. The innervation of the different vessels became increasingly diverse between birth and adulthood, indicating a relationship between the pattern of vascular innervation and local physiological requirements. Factors which could influence age-related changes in nerve pattern and density are discussed.

Adrenergic Fibers↗