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Biomedical subjects

N A Svendgaard

Publications and source records attributed to N A Svendgaard.

52 records · Page 3Linked to original sources

Potentiation and antagonism of serotonin effects on intracranial and extracranial vessels. Possible implications in migraine.

The vasoconstrictor action of serotonin and its interaction with drugs (methysergide, pizotifen, cyproheptadine, ergotamine, dihydroergotamine) that have serotonin-antagonistic properties and that are used in the treatment of migraine were studied on isolated feline and human intracranial and extracranial arteries in vitro. The intracranial vessels were more sensitive to serotonin than the extracranial ones. The serotonin antagonists caused the expected impairment of the serotonin-induced contraction. In minute doses, the various compounds potentiated the contraction produced by serotonin. There is reason to believe that the mechanism responsible for this interaction is selective for tryptaminergic agents. This dual action of the serotonin antagonists may contribute to a beneficial effect in migraine by an interference during both the vasoconstrictory and vasodilatory phase.

Animals↗

Secondary hyperparathyroidism combined with uremia and giant cell containing tumor of the cervical spine. A case report.

A 47-year-old woman with chronic pyelonephritis since 1950 was prepared for hemodialysis or kidney transplantation. Investigation disclosed secondary hyperparathyroidism and an osteolytic lesion in C VII and Th I causing a subluxation. There were minor neurological symptoms and apparent risk of luxation of the cervical spine with resulting injury to the spinal cord. Operation was performed with total parathyroidectomy and excision of the bone tumor, followed by fixation of the cervical spine with bone graft. There were no major complications during the postoperative period and the patient was mobilized four months after the operation.

Cervical Vertebrae↗

Fibromuscular dysplasia of the cervico-cephalic arteries.

Six cases of fibromuscular dysplasia of the cervical and cephalic portions of the internal carotid arteries, including their intracranial branches are reported. It should perhaps be pointed out that one of the cases was from the Sudan. As far as we know, the condition has never before been reported in a male African. The condition was associated with an intracranial aneurysm in four of our cases. To our knowledge only three autopsied cases of fibromuscular dysplasia involving intracranial arteries are on record. In our six cases the diagnosis was based on angiographic evidence, and three of the cases, two with intracranial involvement, were verified post mortem.

Adult↗

Increased sensitivity of the basilar artery to norepinephrine and 5-hydroxytryptamine following experimental subarachnoid hemorrhage.

The reactivity of rabbit basilar artery to norepinephrine and 5-hydroxytryptamine was tested in vitro three days following cisternal injection of 1.0 ml autologous blood to simulate subarachnoid hemorrhage. Following this treatment the artery became three to five times more sensitive to norepinephrine compared with vessels from untreated animals. This was reflected in a parallel shift of the log dose-response curve towards lower concentrations of norepinephrine in a way resembling that seen after cocaine treatment of sympathectomy and interpreted as a prejunctional supersensitivity of the vascular alpha-receptors. The injection of blood also increased the amount of vasoconstriction with 5-hydroxytryptamine to a level which was three times higher than that obtained in untreated vessels. The results suggest one type of mechanism whereby monoamines might be involved in cerebral vasospasm following subarachnoid hemorrhage.

Animals↗

Transplantation of central and peripheral monoamine neurons to the adult rat brain: techniques and conditions for survival.

The conditions for survival of transplants of peripheral and central monoamine neurons in the adult rat brain were studied using fluorescence histochemistry. Pieces of the superior cervical ganglion from newborn and adult rats and CNS tissue containing noradrenaline (NA), dopamine (DA) and indolamine (IA) neurons from embryonic, newborn and adult rats were transplanted to various brain sites using different techniques: insertion of the graft by means of a glass rod, by "injection", or by direct implantation of the graft in a resection cavity. Three principally different locations for the graft were tested: within the brain parenchyma in the caudal diencephalon and the caudate nucleus; onto the dorsal surface of the caudate nucleus; and onto the pial covering in the choroidal fissure after removal of the overlying cortex and parts of the hippocampal formation. Attempts were also made to transplant to the dorsal surface of the caudate nucleus or the hippocampus with the aid of an "artificial" vascular bed, achieved by previous transplantation of an iris. Consistent survival of the transplanted central and peripheral neurons was obtained only when the transplant was placed in contact with a vessel-rich tissue, such as the pia in the choroidal fissure or the "artificial" vascular bed. While the majority of the monoamine-containing neurons in the transplants died within the first month after transplantation, a significant number of neurons (up to about 150 in the ganglionic pieces and up to about 500 in the embryonic or newborn CNS pieces) survived for at least half a year in the brain. Survival of transplanted adult central monoamine neurons was not observed. A substantial outgrowth of axons was observed from all types of neurons in their new location. These newly formed fibers formed extensive fiber patterns within the transplant itself, around pia vessels, and within the adjacent brain tissue, above all in the hippocampal formation. The usefulness of the present transplantation technique for the exploration of mechanisms underlying reformation of axonal connections in the adult mammalian CNS is discussed.

Age Factors↗

Regeneration of central cholinergic neurones in the adult rat brain.

The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together along the deneravated Schwann cell sheaths. From a comparison between the central reinnervation process and the process of reinnervation of the iris by peripheral cholinergic axons after transplantation to the anterior eye chamber, it is concluded that the regenerative capacity of central cholinergic neurones (above all the septo-hippocampal system) is not much inferior to that of their peripheral counterparts when given similar growth conditions. Moreover, central cholinergic neurones seem partly able to replace the peripheral ones in the reinnervation of a denervated peripheral target.

Acetylcholinesterase↗

Reduced noradrenaline uptake and retention in cerebrovascular nerves associated with angiographically visible vasoconstriction following experimental subarachnoid hemorrhage in rabbits.

Rabbits were injected with 1-2 ml autologous blood into the chiasmatic and basal cisterns to stimulate subarachnoid hemorrhage. Selective vertebral angiography performed at various time-periods following blood injection showed a 27 per cent reduction in basilar artery diameter within 3-5 days, followed by normalization so that pre-injection size was regained within 26 days after the treatment. Formaldehyde histofluorescence of the major basal pial arteries showed almost 75 per cent reduction in number and fluorescence intensity of visible perivascular adrenergic nerves at 3-7 days following blood injection. The noradrenaline fluorescence in a normal number of nerves returned to control values at 26 days after treatment. The noradrenaline reduction in the perivascular nerves was confirmed in fluorometric determinations. The presence of cisternal blood markedly impaired the neuronal uptake of 3H-noradrenaline at 3 days following the injection. The transmitter uptake had normalized 2 weeks later. The impaired neuronal uptake of noradrenaline in the presence of cisternal blood is in accordance with the net reduction in transmitter of the perivascular nerves, and may provide one pathophysiological factor in the development of angiographically visible vasoconstriction, having a time-course resembling that of the functional changes in the perivascular adrenergic nerves.

Adrenergic Fibers↗

Subarachnoid haemorrhage in the rat: angiography and fluorescence microscopy of the major cerebral arteries.

A subarachnoid haemorrhage (SAH) in the rat was produced by the injection of blood via a previously implanted catheter connected to the cisterna magna. Repeated angiographical examinations of the vertebro-basilar arteries revealed a biphasic vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at two days after cisternal blood injection. Fluorescence microscopical examination of the major cerebral arteries at day two after the SAH revealed a reduction in the fluorescence intensity and in the number of histochemically visible sympathetic nerve terminals.

Animals↗

Subarachnoid haemorrhage in the rat: effect on the development of vasospasm of selective lesions of the catecholamine systems in the lower brain stem.

Intracisternal injection of blood in the rat produces an angiographically demonstrable biphasic vasospasm. Lesioning at the level of the mesencephalon of the ascending catecholamine pathways from locus coeruleus in the pons and the A1 and A2 nuclei in the medulla oblongata prior to cisternal blood injection prevents the development of both acute and late spasm. Selective lesioning in the medulla oblongata of ascending fibres from A1 and A2 also prevents development of spasm, indicating that these nuclei, which project to the hypothalamus-pituitary, are essential for the spasm syndrome. It is suggested that a substance vasospasm is produced by a substance liberated either by the hypothalamus or by the pituitary is involved in the occurrence of spasm.

Afferent Pathways↗

Subarachnoid haemorrhage in the rat: effect on the development of cerebral vasospasm of lesions in the central serotoninergic and dopaminergic systems.

In the rat an intracisternal injection of blood induces an angiographically demonstrable biphasic cerebral arterial vasospasm. Chemical destruction of the central serotoninergic and dopaminergic pathways prior to the cisternal blood injection does not affect the spasm pattern after the subarachnoid haemorrhage. It is suggested that neither system plays a role in the development of spasm.

5,7-Dihydroxytryptamine↗

Changes in cerebral blood flow and metabolism following intraarterial or local administration of nimodipine, before and after experimental subarachnoid hemorrhage in baboons.

Experimental subarachnoid hemorrhage (SAH) was induced in baboons by repeated injections of autologous blood into cisterna chiasmatis and cisterna magna, a total of 14-33 ml being injected over 3-4 days. Cerebral blood flow (CBF; 133xenon clearance) and cerebral metabolic rate of oxygen (CMRO2) were measured before, and 7 days after, the first blood injection. The effect of the calcium channel blocker, nimodipine, used in a commercially available form for clinical application, was studied following continuous i.a. infusion (0.1 microgram X kg-1 X min-1) for an interval of 45 min, and also 20 and 60 min after intrathecal administration of 1 microgram X kg-1. During the infusion experiments, CBF was increased by 25-30% both before and after the cisternal blood injection. CMRO2 was also enhanced, but much less. Nimodipine in doses given did not alter systemic blood pressure. Following intrathecal application, CBF and CMRO2 slightly increased at 20 min only before experimental SAH.

Animals↗