Decrease in adrenergic axon sprouting in the senescent rat.

When the septal area in young adult rats is denervated by a lesion of the fimbria-fornix, adrenergic fibers proliferate within the denervated area. The same operation performed on aged animals gives rise to a qualitatively similar but quantitatively less pronounced response. This reduction in reactive growth may reflect a decreased capacity of the aged brain to remodel its circuitry and restore lost function.

Supraoptic nucleus of the Brattleboro rat has an altered afferent noradrenergic input.

The distribution of fluorescent varicosities in the supraoptic nucleus of Brattleboro rats was compared to that in normal rats. The Brattleboro rat, which is characterized by a genetic absence of vasopressin, had fewer fluorescent varicosities in apposition to the vasopressin-deficient perikarya. The oxytocin-producing neurons in the same nucleus were hyperinnervated. These data suggest that the target neuron peptide (vasopressin) is necessary for the maintenance of normal noradrenergic innervation patterns.

Nature and nurture in development of the autonomic neuron.

Arguments are presented for the hypothesis that during an early stage of development the cells which become principal neurons of the autonomic nervous system possess information regarding the positions they will occupy within the body. A second stage of development, during which a decision is made regarding which neurotransmitter to employ, is delayed until each neuron has assumed its permanent position in the body and has sampled, presumably via its growing axons, the peripheral field which it will innervate. The development of cholinergic mechanisms takes precedence; adrenergic neurons may develop only when cholinergic sites have been occupied. An extended period during which the differentiation of transmitter mechanisms may be modulated permits the neuron to adequately sample the periphery prior to commitment to a specific transmitter economy.

Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor.

Platelet-activating factor (PAF) is a naturally occurring phospholipid that serves as a critical mediator in diverse biological and pathophysiological processes. In this study of the interactions of PAF with neuronal cells, it was found that PAF increased the intracellular levels of free calcium ions in cells of the clones NG108-15 and PC12. The increase was dependent on extracellular calcium and was inhibited by the antagonistic PAF analog CV-3988 and by the calcium-influx blockers prenylamine and diltiazem. A functional consequence of this interaction was revealed by measuring a PAF-elicited, Ca2+-dependent secretion of adenosine triphosphate from PC12 cells. Exposure of NG108-15 cells for 3 to 4 days to low concentrations of PAF induced neuronal differentiation; higher concentrations were neurotoxic. Thus, by influencing Ca2+ fluxes, PAF may play a physiological role in neuronal development and a pathophysiological role in the degeneration that occurs when neurons are exposed to circulatory factors as a result of trauma, stroke, or spinal cord injury.

Methylazoxymethanol treatment of fetal rats results in abnormally dense noradrenergic innervation of neocortex.

A single injection of methylazoxymethanol in pregnant rats at 15 days of gestation results in severe cortical atrophy in the offspring. In the adult offspring, the neurochemical markers for the cortical gamma-aminobutyric acid-containing neurons are severely reduced, whereas the noradrenergic markers are minimally altered. Immunohistofluorescence microscopy demonstrates a marked increase in the density of noradrenergic axons which have an abnormal pattern of distribution in the atrophic cortex. The results suggest that the central noradrenergic neurons determine the number of axons to be formed early in brain development, but local factors in the terminal field regulate the ultimate distribution of the noradrenergic axons.

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 .

Clonal analysis of the avian neural crest: migration and maturation of mixed neural crest clones injected into host chicken embryos.

Quail neural crest cells were grown in vitro at clonal density for 7 to 10 days. Mixed neural crest colonies and clones (containing both pigmented and unpigmented cells) were implanted into the trunk region of 2 1/2-day-old host chicken embryos by a previously described injection technique (Bronner and Cohen '79). Here we describe the migratory behavior and subsequent phenotypic expression of the injected cells. Unpigmented cells and pigmented cells both migrated along the ventral neural crest pathway; there were, however, some differences in migratory behavior between the two cell types. After 3 days in vivo, unpigmented quail neural crest cells contributed to the sympathetic ganglion, adrenal medulla, and/or aortic plexus in the host. Many of the unpigmented cells became catecholamine-containing neuroblasts. Unpigmented cells were never observed in the gonads or the gut, but localized only in regions normally populated by trunk neural crest precursors to neurons and supportive cells. Melanocytes derived from the same precursor, however, were often found in the gonads or gut, in addition to normal neural crest locations in the trunk. These results demonstrate that quail neural crest cells grown in tissue culture for 7 days or more retain the ability to migrate and contribute to normal neural crest structures when placed in the embryonic environment. Under the conditions described, a single neural crest cell gave rise to daughter cells expressing the melanotic phenotype (detected in tissue culture) and adrenergic phenotypes (detected after injection in vivo). This demonstrates that at least some single cells of the premigratory crest in the trunk region are pluripotent.

Glucocorticoid receptor-immunoreactivity in C1, C2, and C3 adrenergic neurons that project to the hypothalamus or to the spinal cord in the rat.

A combined retrograde transport-double immunohistochemical staining method was used to determine the extent to which rat liver glucocorticoid receptor-immunoreactivity (GR-ir) is contained within phenylethanolamine-N-methyltransferase (PNMT)-ir neurons that project to the paraventricular nucleus of the hypothalamus (PVH) or the spinal cord. The results confirmed that cells in the C1, C2, and C3 adrenergic cell groups each contribute to the adrenergic innervation of the PVH, and indicated that the great majority of retrogradely labeled neurons in each group (80% overall) also express GR-ir. Following injections in the upper thoracic segments of the spinal cord, the bulk of adrenergic neurons that were retrogradely labeled were found in the C1 cell group, though 31% of the total number PNMT-ir cells that could be retrogradely labeled following spinal injections were localized in the C2 and C3 regions. Of these spinally projecting PNMT-ir neurons, 62% displayed GR-ir. The results suggest all three medullary adrenergic cell groups contribute projections to the spinal cord and/or the PVH, and that the capacity to express the GR phenotype is a common, though perhaps not universal, attribute of PNMT-ir neurons. No pronounced differences in the expression GR-ir were observed in adrenergic neurons as a function of their location or efferent projections. Brainstem adrenergic neurons may play a role in integrating neuronal and hormonal controls of adrenal function via ascending and descending projections.

Morphology of sympathetic preganglionic neurons in the thoracic spinal cord of the cat: an intracellular horseradish peroxidase study.

Horseradish peroxidase was intracellularly injected into sympathetic preganglionic neurons (SPN) of the third thoracic segment in cats. Seven neurons were reconstructed from serial horizontal or parasagittal sections of the spinal cord. The cell bodies of all neurons were located in the n. intermediolateralis pars principalis (ILp). They were spindle-shaped with the long axis in craniocaudal direction or large and multipolar or small and oval in shape. Preferentially on the cranial and caudal pole of the cell body, five to eight primary dendrites arose from the cell body. Dendritic branches were traced to their terminations at distances up to 1,330 microns from the cell body. The dendritic fields of all SPNs were strictly oriented in the longitudinal direction with a total length of 1,500-2,540 microns. The cranial and caudal dendritic fields were about equal in length but, with one exception, the degree of branching was always greater in the cranial than in the caudal dendritic field. The dendritic fields of all SPNs were primarily restricted to the ILp. In the mediolateral direction it extended from 130 to 360 microns and in the dorsoventral direction from 50 to 180 microns. Only rarely, a higher-order dendrite left the boundaries of the ILp and projected dorsolaterally or laterally into the white matter or ventromedially or medially into the adjacent n. intercalatus. All dendrites showed various forms of spines. At a distance of 132-437 microns from the cell body the axon arose as a direct extension of a process which closely resembled a primary or second-order dendrite. The axons projected ventrally and mostly caudally along the lateral border of the gray matter until they turned laterally at the end of the ventral horn. No axon collaterals were observed.

Sympathetic and afferent somata projecting in hindlimb nerves and the anatomical organization of the lumbar sympathetic nervous system of the rat.

The anatomy of the sympathetic pathways from the spinal cord to the lumbar sympathetic trunk and the inferior mesenteric ganglion was studied systematically in the rat. Details of the arrangements of white and gray rami communicantes, sympathetic trunk ganglia, the intermesenteric nerve, and the lumbar splanchnic nerves are summarized. A modified nomenclature for the segmental ganglia of the paravertebral sympathetic chain is proposed. Cell bodies of sensory and sympathetic axons projecting to the skin and skeletal muscle of the rat hindlimb were labeled retrogradely with horseradish peroxidase (HRP) in order to study numbers, segmental distribution, and location of the somata of these neurons quantitatively. HRP was applied to the nerves supplying skeletal muscle (gastrocnemius-soleus, GS), hairy skin (sural, SU; saphenous, SA) and to a mixed nerve (tibial, TI). All sensory somata and 96.4% of the sympathetic cell bodies were located ipsilaterally. Sensory somata were commonly restricted to two adjacent dorsal root ganglia (usually L3-4 for SA; L4-5 for GS, TI; L5-6 for SU). Although the sympathetic somata were more widely distributed rostrocaudally (four to six segments), their maximum was always located one or two segments more cranially than the sensory outflow, i.e., corresponding to the rami communicantes grisei. From the data, it is estimated that 420 sympathetic and 530 afferent neurons project into GS, 590 and 3,610 into SU, 920 and 3,750 into SA, and 1,070 and 5,760 into TI. These absolute neuron numbers are compared with electron microscopic fiber counts from the literature.

Innervation of the guinea pig trachea: a quantitative morphological study of intrinsic neurons and extrinsic nerves.

The innervation of the guinea pig trachea was studied in wholemount preparations stained for acetylcholinesterase, catecholamines, and substance P immunoreactivity and by electron microscopy. The majority of parasympathetic and afferent nerve fibres arrive from the vagus via branches of the recurrent laryngeal nerves. The recurrent laryngeal nerves are composed of several fascicles comprising 600-700 small myelinated fibres (2-5 microns diameter) and about 1,000-2,000 unmyelinated fibres; both components exit from the nerve and project in fine branches to the trachea. A separate component of 200-250 large myelinated fibres (more than 5 microns diameter) runs the full length of the nerve and innervates the striated muscles of the larynx. The recurrent laryngeal nerves are slightly asymmetric in their origin, length, number, and composition of fibres, with the right nerve being shorter but with more numerous and thinner myelinated fibres. At the distal end of the recurrent nerve, a fine branch called the ramus anastomoticus connects it to the superior laryngeal nerve. In the tracheal plexus, there are on average 222 ganglion cells (range 166-327), distributed mostly in small ganglia of 12 or fewer neurons. The ganglionated plexus is situated entirely outside the tracheal wall, overlying the smooth muscle. Ligation experiments show that sympathetic nerve fibres reach the trachea with the recurrent nerves via anastomoses between the sympathetic chain and vagus nerves, or occasionally with recurrent nerves directly, the largest being at the level of the ansa subclavia. There are also perivascular sympathetic nerve plexuses. Substance P immunoreactive fibres enter the trachea from the vagus nerves and by pathways similar to those of sympathetic nerves. There are also paraganglion cells within the recurrent laryngeal nerve that contain catecholamines and are surrounded by substance P immunoreactive fibres. After cervical vagotomy, all the large myelinated fibres of the ipsilateral recurrent laryngeal nerve degenerate and so do all but 10 or 20 small myelinated fibres and all but a few unmyelinated fibres. Degenerating fibres are found within the entire tracheal plexus, indicating bilateral innervation. The small myelinated fibres that survive cervical vagotomy probably represent sympathetic or afferent nerves with their cell bodies located in sympathetic or dorsal root ganglia.

5-Hydroxytryptamine demonstrated immunohistochemically in rat cerebrovascular nerves largely represents 5-hydroxytryptamine uptake into sympathetic nerve fibres.

This study has re-examined, by immunohistochemistry, a proposed serotonergic innervation of major cerebral vessels in the rat. Previous studies had demonstrated a dense perivascular plexus of 5-hydroxytryptamine immunoreactive nerve fibres upon major cerebral vessels in this and many other species. The present work has shown, however, that 5-hydroxytryptamine immunoreactive nerve fibres are rarely observed in cerebral vessels prepared by perfusion-fixation in situ, and only form a well-developed plexus in vessels prepared, as in previous studies, by immersion-fixation. Prior treatment with a predominantly noradrenergic uptake inhibitor desmethylimipramine but not the serotonergic uptake inhibitor fluoxetine produced a major diminution in the 5-hydroxytryptamine immunoreactive plexus visualized in these immersion-fixed vessels. In addition, 5-hydroxytryptamine immunoreactive nerves were only occasionally observed in immersion-fixed vessels from animals that had been pretreated with 6-hydroxydopamine to produce adrenergic denervation. The removal, firstly, of vessel-contained blood, by left ventricular perfusion with Krebs' solution, prior to vessel dissection and immersion-fixation, resulted in an absence of 5-hydroxytryptamine immunoreactivity in perivascular nerves. Immunoreactivity could then be restored by briefly incubating vessels in Krebs' solution containing either blood or 5-hydroxytryptamine before fixation. It would appear therefore that 5-hydroxytryptamine is rarely present under normal circumstances in the perivascular nerves of major cerebral vessels, and that previous descriptions of a dense serotonergic nerve plexus represent 5-hydroxytryptamine in blood released during vessel dissection being taken up via the noradrenaline-uptake system into perivascular sympathetic nerves. The possibility is thus raised that 5-hydroxytryptamine uptake and interaction within perivascular adrenergic nerves could occur in those cerebrovascular disorders where blood is released.

Interaction between adrenergic fibers and intermediate cholinergic neurons in the rat spinal cord: a new double-immunostaining method for correlated light and electron microscopic observations.

Relationships between cholinergic neurons and adrenergic fibers in the intermediate region of the rat thoracic spinal cord were examined using a new immunohistochemical double-staining method for light and electron microscopic observations. Cholinergic neurons were labeled by a monoclonal antibody to choline acetyltransferase and stained bluish green by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside reaction products using beta-galactosidase as a marker. On the same sections, adrenergic fibers were labeled by a polyclonal antiserum to phenyl-ethanolamine-N-methyltransferase and stained brown by diaminobenzidine reaction products using peroxidase as a marker. After embedding in Epon, the sections were examined in the light and electron microscopes. In the light microscope, choline acetyltransferase-like immunoreactive cells were seen in the four discrete areas of the intermediate region: the principal intermediolateral nucleus, the central autonomic nucleus, the intercalated nucleus and the funicular intermediolateral nucleus. These cell groups seemed to be connected to each other by their processes, and they showed a "ladder-like appearance" as a whole. Phenylethanolamine-N-methyltransferase-like immunoreactive fibers were present only along this "ladder-like structure" and were the most rich in the principal intermediolateral nucleus. In the electron microscope, some of the choline acetyltransferase-like immunoreactive neurons, which were identified by light micrographs, were found to receive synaptic inputs from phenylethanolamine-N-methyltransferase-like immunoreactive boutons in the principal intermediolateral nucleus. These findings suggest that the adrenergic axons in the principal intermediolateral nucleus directly affect the activity of the cholinergic preganglionic sympathetic neurons.

Electrophysiological characterization of putative C1 adrenergic neurons in the rat.

Recent studies in the rat have demonstrated that at least two populations of sympathoexcitatory reticulospinal neurons reside in the nucleus reticularis rostroventrolateralis. It appears that only one of these populations consists of C1 adrenergic neurons. The present study used both double-labeling (one retrograde tracer and immunohistochemistry) and triple-labeling (two retrograde tracers and immunohistochemistry) to determine if C1 adrenergic neurons, which are immunoreactive for phenylethanolamine N-methyltransferase, exhibit a projection pattern that is sufficiently unique to permit the electrophysiological discrimination between C1 adrenergic and non-adrenergic neurons in the nucleus reticularis rostroventrolateralis. Double-labeling experiments indicated that 71% (range: 53-80) of phenylethanolamine-N-methyltransferase-immunoreactive neurons in the nucleus reticularis rostroventrolateralis could be retrogradely labeled from the thoracic cord, as were 76% (range: 67-94) following tracer injection in the central tegmental tract at pontine levels. Triple-labeling experiments indicated that 88% (range: 82-93) of nucleus reticularis rostroventrolateralis neurons with projections to both spinal cord and central tegmental tract were phenylethanolamine-N-methyltransferase-immunoreactive. Single-unit recording, in nucleus reticularis rostroventrolateralis, was used to identify antidromic potentials elicted from stimulation sites in the spinal cord and/or central tegmental tract. Since clonidine is known to reduce central adrenaline turnover, sensitivity to this drug was used to identify putative adrenergic neurons. Twenty-six nucleus reticularis rostroventrolateralis neurons with axonal projections to both the ipsilateral spinal cord and the central tegmental tract were recorded in halothane-anesthetized rats. All these cells were barosensitive, pulse-modulated, and 16 of the 16 cells tested exhibited a 66 +/- 8% reduction in activity upon the intravenous administration of clonidine (20 micrograms/kg). Most (13 out of 16) exhibited a strong respiratory modulation. The conduction velocity of their spinal collateral was generally low (0.9 +/- 0.1 m/s) and their firing rate moderate (7.4 +/- 1.2 spikes/s). Forty-three nucleus reticularis rostroventrolateralis cells with axonal projections exclusively to the thoracic cord were studied for comparison. These cells were strongly barosensitive and pulse-synchronous, had a high discharge rate (25 +/- 3 spikes/s) and a moderate conduction velocity (3.4 +/- 0.3 m/s). Only one of the 15 cells tested was inhibited by clonidine and only two to these 15 cells exhibited a detectable respiratory modulation. Thus barosensitive nucleus reticularis rostroventrolateralis neurons with axonal projections to both the spinal cord and the central tegmental tract likely belong to the C1 adrenergic cell group. It is concluded that this subgroup of adrenergic neurons probably subserves a vasomotor function.

Comparison of transmitter release properties of embryonic sympathetic neurons growing in vivo and in vitro.

The functional behavior of embryonic chick sympathetic neurons was determined by inducing release of [3H]norepinephrine by electrical stimulation of sympathetic neurons growing in the chick heart and in culture, with and without heart cells. A very close correspondence between the functional behavior of neurons developing with the heart cells, either in vivo or in vitro, was demonstrated. For example, the outflow of tritium from [3H]norepinephrine loaded sympathetic neurons of 15-day-old chick heart was about three times more at 10 Hz than at 1 Hz. In contrast, the outflow of tritium from 12-day-old [3H]norepinephrine loaded cultured sympathetic neurons was inversely related to the frequency of stimulation (outflow at 1 Hz was about three time more than at 10 Hz). When neurons were co-cultured with the heart cells, the frequency-outflow relationship reverted to that seen in the intact heart. Electrically-evoked outflow of tritium from the heart was reduced in a concentration-dependent manner by 3-30 nM tetrodotoxin, abolished in 0.25 mM Ca medium, and potentiated by 3 mM tetraethylammonium. In sharp contrast, the outflow evoked by stimulation of cultured neurons was neither blocked by 30-300 nM tetrodotoxin, low Ca, nor potentiated by tetraethylammonium. However, when neurons were co-cultured with heart cells, the evoked outflow was blocked by 30 nM tetrodotoxin and low Ca, and potentiated by tetraethylammonium. Veratrine (10 microM) had very little effect on the outflow from cultured neurons but induced a massive outflow from co-cultures as well as hearts. Neurons grown in a medium conditioned by the heart cells were not sensitive to tetrodotoxin and veratrine. It is implied that cultured sympathetic neurons are endowed mostly with Ca channels, and that the Na channels become functional only when neurons are grown with the target cells. This dramatic alteration in the functional behavior of neurons co-cultured with heart cells indicates that the effector organ has an important role in the development of ionic conductances of sympathetic neurons growing in the body and in culture.

Demonstration of adrenergic and dopaminergic receptors in cultured sympathetic neurons--their coupling to cAMP but not to the transmitter release process.

Experiments were carried out on cultured sympathetic neurons of the chick embryo; first, to demonstrate the presence of adrenergic and dopaminergic receptors, and then to see if these receptors are involved in regulation of transmitter release. We show that alpha 2-agonists, norepinephrine, epinephrine and clonidine, had no effect on neuronal cyclic 3',5'-adenosine monophosphate content. Forskolin enhanced neuronal cyclic 3',5'-adenosine monophosphate from a control value of about 20 pmoles/mg protein to 150 pmoles/mg protein. In the presence of alpha 2-agonists and forskolin the cyclic 3,5'-adenosine monophosphate content increased between 340 and 430 pmoles/mg protein. The alpha 1-agonist, phenylephrine, had no such effect. The facilitatory effect of alpha 2-agonist on forskolin-stimulated cyclic 3',5'-adenosine monophosphate production was blocked by the alpha 2-antagonist, yohimbine, but not the alpha 1-agonist, prazosin. Dopamine did not affect neuronal cyclic 3',5'-adenosine monophosphate content, but forskolin-stimulated increase in cyclic 3',5'-adenosine monophosphate was further facilitated by dopamine, and this effect was blocked by haloperidol. Activation of neuronal alpha 2-receptors by norepinephrine, epinephrine and clonidine did not interfere with electrically induced release of tritium from [3H]-norepinephrine-loaded sympathetic neurons. However, if sympathetic neurons were co-cultured with heart cells, clonidine, norepinephrine and epinephrine markedly inhibited the stimulation-induced release. Yohimbine or phentolamine partially reversed the inhibitory effects of alpha 2-agonists. alpha 2-Agonists and -antagonists also modified stimulation-induced release of tritium from [3H]norepinephrine-loaded hearts of the chick embryo.(ABSTRACT TRUNCATED AT 250 WORDS)

The allocation of nerve fibres to the anterior eye segment and peripheral ganglia of rats. II. The sympathetic innervation.

The sympathetic innervation of the peripheral ganglia related to the eye, i.e. the trigeminal ganglion, the ciliary ganglion and the pterygopalatine ganglion, and of the anterior eye segment was studied in rats. Selective labelling of sympathetic nerves was obtained by means of injection of [3H]leucine into the superior cervical ganglion. Bundles of sympathetic nerve fibres were found in the trigeminal ganglion and the pterygopalatine ganglion but were absent in the ciliary ganglion. In addition individual sympathetic nerve fibres, which may have contacts with trigeminal ganglion cells, were found between the ganglion cell bodies all over the trigeminal ganglion indicating a sympathetic innervation of this ganglion. In the anterior eye segment, there appeared to be a sympathetic innervation of the ciliary cleft, the ciliary body and the iris. Within the ciliary body sympathetic nerve fibres innervate the central stroma and the stroma of the ciliary processes. Labelled sympathetic nerve fibres were also observed in the stroma of the iris and were most abundant in its periphery. Most sympathetic fibres reach the iris and ciliary body by way of the base of the ciliary body. Only few sympathetic fibres are present in the ciliary cleft. No sympathetic innervation of the cornea was found.

Adrenergic projection from the caudal part of the nucleus of the tractus solitarius to the parabrachial nucleus in the rat: immunocytochemical study combined with a retrograde tracing method.

The presence of an adrenergic projection from the nucleus of the tractus solitarius (NTS) to the parabrachial nucleus (PB) was demonstrated by the immunocytochemistry combined with a retrograde tracing method. Numerous neurons containing both phenylethanolamine N-methyltransferase, a marker for adrenaline, and wheat germ agglutinin-conjugated horseradish peroxidase, a retrograde tracer, were detected in the dorsolateral part of the NTS at the level of the area postrema after injection of the tracer into the dorsal PB.

Directional growth of sympathetic nerve fibres in vitro towards enteric smooth muscle and heart from mice with congenital aganglionic colon and their normal littermates.

Neuronotrophic factors in tissues from normal mice and mice with hereditary aganglionic colon (s1/s1) were assayed by examining neurite extension in vitro from sympathetic ganglia (superior cervical and coeliac) towards explants of stomach, atrium and colon in co-culture. Directional growth of neurites from both ganglia towards all 3 target explants was observed. There were no statistically significant differences between normal and s1/s1 ganglia in the capacity to extend neurites, neither were there differences between the target tissues of these mice in ability to promote neurite extension from ganglia. Since it is known that in s1/s1 mice there is impaired migration of neuroblasts along the developing gut, we conclude that the mechanisms determining neurite extension in culture are different to those regulating neuroblast migration and early differentiation. Studies on normal mice revealed that antiserum to nerve growth factor (NGF) blocked the outgrowth of neurites towards atrium, and reduced but did not abolish the outgrowth towards stomach, suggesting that the gut muscle produces a factor trophic for sympathetic neurones which is immunochemically distinguishable from NGF.

Long-term effects of superior cervical ganglionectomy on cortical blood flow of non-anesthetized rabbits in resting and hypertensive conditions.

The long-term effects of sympathectomy on cerebral cortical blood flow (CBF) were studied in the conscious rabbit. The quantitative, repeated measurements of blood flow were made by determination of helium clearance by mass spectrometry and were obtained simultaneously with measurements of local tissue pO2 and pCO2. Eight to 10 weeks after unilateral sympathectomy, resting blood flow in the homolateral cortex was decreased by a mean of 17% compared to the heterolateral cortex. In two animals in which blood flow was recorded both before and after the sympathectomy, the same phenomenon was observed from 8 to 30 days after the operation. The response to i.v. infusion of noradrenaline was identical in both hemispheres: doses inducing a 40% rise in blood pressure did not significantly modify CBF. The responses to angiotensin II-induced hypertension were also identical. Histochemical verifications demonstrated the effectiveness of the denervation in the pial arteries and the intraparenchymal arteries in the region studied. Thus the decrease in CBF induced by chronic sympathectomy cannot be attributed to the development of hypersensitivity to catecholamines. This decrease remained stable whatever the value of resting flow and was maintained under anesthesia. It is concluded that, as in the peripheral circulation, chronic sympathectomy affects the equilibrium of the vascular smooth muscle fibers, but that circulating amines play no compensatory role in the cerebral circulation because of the blood-brain barrier.