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Biomedical subjects

A S Zagami

Publications and source records attributed to A S Zagami.

At least 19 recordsLinked to original sources
PubMed2002

Suppression by eletriptan of the activation of trigeminovascular sensory neurons by glyceryl trinitrate.

The effect of intracarotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate vascular headache, on the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Cats were anaesthetised with alpha-chloralose, immobilised and artificially ventilated. The superior sagittal sinus (SSS) was isolated and stimulated electrically. Facial receptive fields (RF) were also stimulated. Single neurons were recorded from the trigeminal nucleus caudalis with a metal microelectrode equipped with six glass barrels for microiontophoresis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (mean rate 19+/-7, range 5-100 microg kg(-1) min(-1), in a volume of 2 ml min(-1)) increased the spontaneous discharge rate of second-order neurons which received dural and facial sensory input to 429+/-80% of control. Iontophoretic application of the 5-HT(1B/1D) receptor agonist eletriptan (50 nA) at the peak of the response decreased the discharge rate of neurons towards pre-GTN control levels. In the presence of continuous iontophoretic application of the 5-HT(1B/1D) receptor antagonist GR127935, the decrease in discharge rate caused by eletriptan was antagonised. We conclude (1) that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN and (2) that the antimigraine agent eletriptan is able to selectively suppress noxious sensory information from the dura, induced by GTN, via an action at 5-HT(1B/1D) receptors.

Animals↗
PubMed2001

Ophthalmoplegic migraine: a recurrent demyelinating neuropathy?

The demonstration by magnetic resonance imaging (MRI) scanning of thickening and enhancement of the cisternal part of the oculomotor nerve in patients diagnosed as "ophthalmoplegic migraine" prompts reconsideration of this uncommon disorder. The case histories of five patients, three male and two female, varying in age from 6 to 30 years, are presented here. Recurrent painful ophthalmoplegia started in infancy in two cases, childhood in two instances and adult life in one. One child had his first attacks at 3, 5 and 12 months of age, on each occasion 10 days after an injection of triple vaccine. The possibility of this condition being a recurrent demyelinating neuropathy is considered and its possible relationship to migraine explored.

Adolescent↗
PubMed2000

Activation of trigeminovascular neurons by glyceryl trinitrate.

The effect of intra-carotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate headache, including migraine, upon the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Second-order craniovascular neurons which received sensory input from the superior sagittal sinus were recorded in the trigeminal nucleus caudalis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (100 microg kg(-1) min(-1) in a volume of 2 ml min(-1)) increased the mean basal discharge rate of all second-order neurons to 239+/-47% of control. GTN produced a fall in mean blood pressure, but there was no correlation between this fall and the changes in discharge rate. GTN infusions sensitised neurons to the effects of electrical stimulation of the superior sagittal sinus, but not to subsequent GTN infusions. Infusions of similar volumes of vehicle did not alter the discharge rate of neurons. We conclude that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN.

Animals↗
PubMed2000

5-HT(1A) and 5-HT(1B/1D) receptors are involved in the modulation of the trigeminovascular system of the cat: a microiontophoretic study.

Electrical stimulation of the superior sagittal sinus in the cat activated neurones in the trigeminal nucleus caudalis. The mean latency of these responses (10.1 ms) was consistent with activation of Adelta-fibres. Microiontophoretic ejection of either the selective serotonin(1A) (5-HT(1A)) agonist (+)8-OH-DPAT or the 5-HT(1B/1D) agonist alniditan resulted in the reversible suppression of the response to superior sagittal sinus stimulation of 29/46 and 18/20 trigeminal neurones, respectively. The response to sagittal sinus stimulation was suppressed by 39+/-5% (n=46) by (+)8-OH-DPAT and 65+/-5% (n=20) by alniditan. Microiontophoretic ejection of the selective 5-HT(1A) receptor antagonist WAY-100635 significantly antagonised the effect of (+)8-OH-DPAT (effect reduced by 30%, P<0.05). The ejection of GR-127935, a selective 5-HT(1B/1D), antagonist, significantly antagonised the effect of alniditan (effect reduced by 52%, P<0.02). In eight neurones the response to convergent facial receptive field stimulation was also tested in the presence of alniditan. Only 4/8 receptive field responses were suppressed by alniditan (compared to 8/8 sagittal sinus responses) and alniditan had significantly less quantitative effect on the response to receptive field stimulation than on the response to sagittal sinus stimulation in the same neurones (mean reduction 36+/-14% and 66+/-8%, respectively, P<0.05). These results suggest that pharmacological modulation of the trigeminovascular system can occur at the first central synapse and that, in addition to 5-HT(1B/1D) receptors, 5-HT(1A) receptors may be involved in the modulation of sensory neurotransmission in the trigeminovascular system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Effect of cortical spreading depression on activity of trigeminovascular sensory neurons.

The effect of cortical spreading depression, a proposed initiating event for migraine pain, on cortical blood flow (laser Doppler method) and on the spontaneous firing rate and stimulus-evoked responses of trigemino-cervical neurons with craniovascular input was studied in 17 neurons in 8 cats anesthetized with chloralose. Cortical spreading depression, induced via cortical pinprick injury, produced an initial wave of cortical hyperemia (243+/-57% of control) and a later and smaller phase of oligemia (96+/-4% of control). Neither the basal discharge rate (6.7+/-1.7 sec(-1)) nor the evoked responses to electrical stimulation of the superior sagittal sinus (4.1+/-0.8 discharges per stimulus) of upper cervical spinal cord neurons was altered over periods of up to 2 h following one, two, or three waves of spreading cortical depression. We conclude that a small number of episodes of cortical spreading depression is not capable of activating C2 cervical spinal cord craniovascular sensory neurons in the cat.

Animals↗
PubMed1999

Serotonin infusions inhibit sensory input from the dural vasculature.

Intravenous infusions of serotonin (5-hydroxtryptamine creatinine sulphate, 5HT, 50-300 microg/kg/min) in cats reversibly inhibited the responses of cervical spinal cord neurons to electrical stimulation of the superior sagittal sinus. Inhibition developed over 20-30 min and resolved over the same time course, suggesting a dependence on accumulation of 5HT in the central nervous system. Inhibition was suppressed by prior intravenous injection of the 5HT antagonists methysergide (1 mg/kg) and methiothepin (1 mg/kg). Infusions of 5HT (50 microg/kg/min) caused a rise in whole blood levels of 5HT by a factor of 1.5 of control values. 5HT levels in platelet-free plasma rose by a factor of 50. Levels of 5HT and 5 hydroxyindole acetic acid released into the cerebrospinal fluid rose significantly. The results suggest that earlier clinical observations that 5HT infusions can ameliorate the pain of migraine may not have been due to cranial vasoconstriction alone, but could have involved a central action of 5HT.

Action Potentials↗
PubMed1999

Stimulation of the middle meningeal artery leads to Fos expression in the trigeminocervical nucleus: a comparative study of monkey and cat.

The pain of a migraine attack is often described as unilateral, with a throbbing or pulsating quality. The middle meningeal artery (MMA) is the largest artery supplying the dura mater, is paired, and pain-producing in humans. This artery, or its branches, and other large intracranial extracerebral vessels have been implicated in the pathophysiology of migraine by theories suggesting neurogenic inflammation or cranial vasodilatation, or both, as explanations for the pain of migraine. Having previously studied in detail the distribution of the second order neurons that are involved in the transmission of nociceptive signals from intracranial venous sinuses, we sought to compare the distribution of second order neurons from a pain-producing intracranial artery in both monkey and cat. By electrically stimulating the middle meningeal artery in these species and using immunohistochemical detection of the proto-oncogene Fos as a marker of neuronal activation, we have mapped the sites of the central trigeminal neurons which may be involved in transmission of nociception from intracranial extracerebral arteries. Ten cats and 3 monkeys were anaesthetised with alpha-chloralose and the middle meningeal artery was isolated following a temporal craniotomy. The animals were maintained under stable anaesthesia for 24 h to allow Fos expression due to the initial surgery to dissipate. Following the rest period, the vessel was carefully lifted onto hook electrodes, and then left alone in control animals (cat n = 3), or stimulated (cat n = 6, monkey n = 3). Stimulation of the left middle meningeal artery evoked Fos expression in the trigeminocervical nucleus, consisting of the dorsal horn of the caudal medulla and upper 2 divisions of the cervical spinal cord, on both the ipsilateral and contralateral sides. Cats had larger amounts of Fos expressed on the ipsilateral than on the contralateral side. Fos expression in the caudal nucleus tractus solitarius and its caudal extension in lamina X of the spinal cord was seen bilaterally in response to middle meningeal artery stimulation. This study demonstrates a comparable anatomical distribution of Fos activation between cat and monkey and, when compared with previous studies, between this arterial structure and the superior sagittal sinus. These data add to the overall picture of the trigeminovascular innervation of the intracranial pain-producing vessels showing marked anatomical overlap which is consistent with the often poorly localised pain of migraine.

Animals↗
PubMed1998

Meningeal involvement in Wegener's granulomatosis.

We describe a rare neurological manifestation of Wegener's granulomatosis, meningeal involvement, which occurred despite therapy resulting in disease quiescence in other organs. Clinical, radiographic, and neuropathological features are described.

Anti-Inflammatory Agents↗
PubMed1997

311C90: long-term efficacy and tolerability profile for the acute treatment of migraine. International 311C90 Long-Term Study Group.

311C90 (Zomig; zolmitriptan) is a novel, selective serotonin (5HT)1B/1D receptor agonist with both central and peripheral activity, now in late-stage clinical development for acute oral treatment of migraine. Several studies have demonstrated the tolerability and efficacy of 311C90 in the treatment of a single migraine headache. The objectives of this open-label study were to assess the tolerability and efficacy of repeated doses of 5 mg of 311C90 for acute treatment of multiple attacks for up to 1 year. Patients were allowed to treat as many migraine headaches (mild, moderate, or severe) as desired with an initial dose. A second 5-mg dose could be used to treat recurrence should it develop. Safety assessments included ECG, the frequency, intensity, and duration of adverse experiences, and routine hematology, urinalysis, and clinical chemistry parameters. Efficacy assessments included headache severity at 2 hours (i.e., severe, moderate, mild, or none), the proportion of patients pain-free at 2 hours, the use of a second tablet to treat headache recurrence if it developed, and the consistency of these findings over time. The efficacy profile and the nature/incidence of adverse events reported appear to be consistent with previous 311C90 studies. The dosing regimen was well tolerated during multiple exposures. Notably, headache response rates were consistently good after both initial and repeated exposure (> 80% across 1 to 30 attacks). For 67% of patients who treated at least five attacks, 311C90 was effective 80 to 100% of the time.

Adolescent↗
PubMed1996

Mechanisms of oral-pharyngeal dysphagia in patients with Parkinson's disease.

BACKGROUND & AIMS: Oral-pharyngeal dysphagia in Parkinson's disease is well recognized. The aim of this study was to establish the mechanisms of oral-pharyngeal dysphagia in these patients. METHODS: Using simultaneous videoradiography and pharyngeal manometry, we studied 19 patients with Parkinson's disease (12 with oral-pharyngeal dysphagia and 7 without oral-pharyngeal dysphagia) and compared them with 23 healthy controls. RESULTS: the clinical severity of Parkinson's disease predicted neither the presence nor the severity of dysphagia. Minor alterations in oral function were common in controls and patients, but pharyngeal dysfunction was significantly more prevalent in patients. Incomplete upper esophageal sphincter (UES) relaxation was present in 4 patients (21%), all of whom showed increased hypopharyngeal intrabolus pressure, but not all of whom had a diminished UES opening. The patients had a reduced UES diameter (P = 0.004) and a higher intrabolus pressure compared with the controls (P = 0.007). Pharyngeal contraction pressures were lower in patients, but 6 patients with dysphagia and an abnormal pharyngeal wall motion had normal peak pressures. CONCLUSIONS: An incomplete UES relaxation and a reduced UES opening, both associated with high intrabolus pressure, are prevalent in Parkinson's disease. Oral-pharyngeal dysphagia in Parkinson's disease is multifactorial, with the majority of patients showing oral and pharyngeal dysfunction, even before the clinical expression of dysphagia. Impaired pharyngeal bolus transport is the major determinant of dysphagia.

Aged↗
PubMed1994

Pathophysiology of migraine and tension-type headache.

Cortical spreading depression is probably the event underlying the aura of migraine, and biochemical and other studies suggest that a state of increased excitability of central neurons may lead to development and propagation of cortical spreading depression. Anatomical studies delineate some of the sites involved in the central processing of craniovascular nociception. 5-Hydroxytryptamine receptors, particularly 5-HT1, exist at both neural and vascular sites and are implicated in the pathogenesis of migraine. Studies in tension-type headache suggest that its pathogenesis is multifactorial, with contributions from both central and peripheral factors.

Animals↗
PubMed1993

Delayed neurological deterioration following carbon monoxide poisoning: MRI findings.

We present two patients with delayed neurological deterioration following apparent recovery from carbon monoxide poisoning in whom magnetic resonance imaging showed abnormalities. In the first patient, cortical grey matter abnormalities were seen without white matter changes. Visual evoked potentials were, however, abnormal. In the second, diffuse white matter lesions were detected. In neither patient were basal ganglia lesions seen.

Adult↗
PubMed1992

The spinal cord processing of input from the superior sagittal sinus: pathway and modulation by ergot alkaloids.

The effects of ergot alkaloids on field potentials and unit responses produced in the upper cervical spinal cord by stimulation of the superior sagittal sinus (SSS) were examined in 57 anesthetized cats. Electrical stimulation of the SSS produced field potentials and single-unit responses at latencies of 5-20 ms. Field potentials were abolished by section of the first division of the trigeminal nerve but were unaffected or increased by section of the upper cervical nerves. Field potentials were reduced or abolished by intravenous injection of ergotamine or dihydroergotamine (DHE). The evoked response of 41 units (34.4%) were suppressed by either i.v. or iontophoretic administration of ergotamine, DHE or ergometrine. The results suggest that ergot alkaloids exert an effect at a spinal cord relay centre which receives trigeminally mediated input from cranial blood vessels.

Action Potentials↗
PubMed1992

Craniovascular nociceptive pathways relay in the upper cervical spinal cord in the cat.

Units in the dorsolateral area of the upper cervical cord and the ventroposteromedial nucleus of the thalamus respond to stimulation of cranial vessels. To study the physiological role of the upper cervical cord in craniovascular transmission, we used a cryoprobe to interrupt reversibly neural transmission through the cord while recording in the thalamus. Twenty-one of 47 thalamic units tested showed reversible diminution in their response to superior sagittal sinus stimulation during cervical cord cooling. In contrast, receptive field responses and spontaneous thalamic activity were unaffected. These data suggest offt the cervical cord relays craniovascular nociceptive afferents.

Animals↗