Endothelin-1-induced endothelin-1 release causes cerebral vasospasm in-vivo.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M Zuccarello
Publications and source records attributed to M Zuccarello.
Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1.
The purpose of this study was to test whether endothelium-dependent relaxation is decreased during acute vasospasm following subarachnoid hemorrhage (SAH) and the mechanism underlying the decrease. Basilar artery in situ was 35% constricted 3 days following injection of autologous arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), relaxed resting and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT-contracted vasospastic vessels. In contrast, the relaxant potency and efficacy of ACh was similar in control and vasospastic vessels contracted with 5-HT in vitro. In situ suffusion with the ETA-receptor antagonist, BQ-123 (1 microM), reversed the vasospasm by 51% and restored the magnitude of ACh relaxation of vasospastic and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in vitro relaxed endothelin-1 (ET-1)-contracted control vessels to a smaller magnitude than 5-HT-contracted control vessels. These results suggest, in contrast to previous studies, that endothelium-dependent relaxation is decreased during acute vasospasm following SAH. The decreased endothelium-dependent relaxation is secondary to the underlying ET-1-mediated spasm. The inhibition of endothelium-dependent relaxation observed in situ following SAH cannot be demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.
Acetylcholine↗
[Not Available].
We report a case of oro-pharyngeal and oesophageal ulcerative disease in a AIDS patient. The patient complained of severe oral pain and dysphagia. Systemic manifestations as fever and fatigue were also present. Repeated microbiological exams were negative and therapy with either antibiotics or antiviral agents or corticosteroids or colchicine was unsuccessful. Thus, we started thalidomide: 200 mg/day X 21 days, followed by 100 mg/day X 25 days. A dramatic reduction of symptoms was observed within 15 days from the onset of treatment. The healing of ulcers was evident already one month after the start of therapy. No relevant side effects were reported. Among those patients with AIDS at low risk of side effects, thalidomide may represent a successful therapeutic presidium for severe ulcerative disease of the gastrointestinal tract.
English Abstract↗
Endothelin ETA and ETB receptors in subarachnoid hemorrhage-induced cerebral vasospasm.
The relative roles of endothelin ETA and ETB receptor activation in cerebral vasospasm following subarachnoid hemorrhage were investigated in the rabbit. The endothelin ETA receptor antagonist, BQ610 (1 microM; homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp-OH), and the endothelin ETA/ETB receptor antagonist, PD145065 (1 microM; Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp), relaxed the vasospastic basilar artery in situ by 45% and 87%, respectively. These results suggest that subarachnoid hemorrhage-induced vasospasm of the rabbit basilar artery is due to activation of both endothelin ETA and ETB receptors.
Amino Acid Sequence↗
Nitric oxide synthase immunoreactivity in the rat dura mater.
The dura mater has been implicated as a tissue where vascular headache develops. Identification of the neural components of this tissue is a prerequisite for understanding the mechanisms of this pathological process. The nitric oxide molecule, a potent vasodilator, may contribute to the vascular headache process by dilating dural vasculature. Our immunohistochemical study using nitric oxide synthase (NOS) antibodies revealed NOS-positive nerve fibers and a prominent mast cell population in the rat dura. A majority of the immunopositive fibers were associated with the anterior meningeal artery and its branches and sparse innervation with the middle meningeal artery, its branches, and superior sagittal sinus. We propose that the NOS-positive nerve fibers and mast cells be considered as possible participants in the pathogenesis of vascular headache.
Amino Acid Oxidoreductases↗
Brain metastasis from endometrial carcinoma. Report of two cases.
The authors report two cases of surgically treated brain metastases from endometrial cancer which are quite unusual occurrences. In one of them the brain lesion was the presenting symptom of malignancy while in the other the metastasis was discovered after the primary tumor had been treated. Both the brain lesions were scarcely differentiated adenocarcinomas which closely resembled the uterine primaries histologically. The authors review the four cases reported in the literature and discuss the clinical features and the treatment of this disease. The analysis of cases shows that the metastatic potential of endometrial cancer is extremely variable and unpredictable but less severe than that observed in ovarian or cervical tumors. The authors suggest that the erratic behaviour of endometrial cancer may justify an aggressive (though necessarily palliative) approach to brain metastases even in the presence of circumscribed metastatic involvement.
Adenocarcinoma, Papillary↗
Effect of subarachnoid haemorrhage on trigeminovascular calcitonin-gene-related peptide and substance P of the rat dura mater versus cerebral vasculature.
While the presence of a robust perivascular neural network accompanying cerebral and dural blood vessels that contain various neuropeptides is well documented, the functional significance of this innervation is unclear. Following experimentally induced subarachnoid haemorrhage (SAH) in animal models, immunocytochemical studies have revealed that changes occur in the staining intensity of some of these neuropeptides. This study compared the immunostaining intensity of calcitonin-gene-related peptide (CGRP) and substance P (SP) in cerebral and dural perivascular nerve fibers after SAH in the rat. Subarachnoid haemorrhage was produced by injecting 0.3 ml of autologous blood into the cisterna magna of male Sprague Dawley rats. Sham operated animals received an equal volume of buffered lactated Ringer's solution (pH 7.4). Changes in the immunostaining intensity of cerebral and dural vessels were evaluated by independent observers at 6, 24, and 48 hours after SAH. Immunostaining of CGRP was reduced in cerebral vessels at 6 hours and returned to normal by 48 hours. In contrast, CGRP immunostaining of dural perivascular nerve fibers was unchanged at all time periods examined. A marked decrease in SP immunostaining was documented at 6 hours in both the cerebral and dural vessels in all animals; at 48 hours, the staining intensity had returned to control levels. These results support the idea that several subpopulations of trigeminovascular neurons containing CGRP, SP, or both project to cerebral and dural vessels. Since these subpopulations may be differentially activated in pathologic conditions, such as SAH or vascular headache, the potential exists for pharmacologic intervention of specific neuropeptides with the resultant abatement of a pathologic process.
Animals↗
Effect of remacemide hydrochloride on subarachnoid hemorrhage-induced vasospasm in rabbits.
The purpose of this study was to assess the role of an excitatory amino acid (EAA) receptor antagonist (remacemide hydrochloride) in a rabbit model of subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. Cerebral angiograms were performed on 22 rabbits pre-SAH and 72 h post-SAH: 6 rabbits received an injection of mock cerebrospinal fluid (1 ml/kg) into the cisterna magna (group I, the control group); 6 rabbits were subjected to SAH but received no treatment (group II); autologous blood (1 ml/kg) from the central ear artery was injected into the cisterna magna of these rabbits; 6 rabbits were subjected to SAH (1 ml/kg) and treated with intraperitoneal (IP) bolus injections of remacemide hydrochloride (15 mg/kg) every 12 h beginning 30 minutes after SAH (group III); and 4 rabbits were not subjected to SAH but received IP bolus injections of remacemide hydrochloride every 12 h (group IV). Digital subtraction angiography was used to measure the diameter of the basilar artery. At 72 h post-SAH, vasospasm was evident in all untreated rabbits. The diameter of the basilar artery was reduced significantly below pre-SAH levels by 35.3 +/- 5.8% (mean +/- standard error of the mean). Treatment with remacemide hydrochloride significantly ameliorated vasospasm (27.3 +/- 5.4%, p < 0.001). These findings suggest that in this model EAAs may cooperate in the genesis of SAH-induced cerebral vasospasm and that NMDA receptor antagonism with remacemide hydrochloride can partially prevent the SAH-induced vasospasm of a large cerebral artery.
Acetamides↗
Serotonin (5-HT) fibers of the rat dura mater: 5-HT-positive, but not authentic serotoninergic, tryptophan hydroxylase-like fibers.
Serotonin (5-HT)-positive, but not tryptophan-5-hydroxylase (TPOH)-positive, authentic serotoninergic fibers were shown in the rat dura mater. 5-HT immunoreactive fibers in the dura are postulated to result from 5-HT uptake from circulating blood elements (e.g. platelets, mast cells) by perivascular sympathetic nerve fibers. A robust TPOH-immunoreactive mast cell population was identified in the dura; this result confirms the TPOH antibody specificity to cells known to synthesize 5-HT. While these results indicate that there are no authentic serotoninergic fibers in the dura mater, the mast cells, platelets and cerebrospinal fluid can serve as a source of 5-HT activating 5-HT receptors known to be present in this tissue.
Animals↗
Dural neuropeptide changes after subarachnoid hemorrhage in rats.
The effect of subarachnoid hemorrhage (SAH) on the neuropeptides and mast cells of the rat dura mater has not been reported. We examined the outcome of SAH on the rat supratentorial dura mater to determine whether dural nerves undergo effects similar to those of nerves accompanying cerebral blood vessels after SAH. Following the injection of fresh autologous arterial blood into the cisterna magna, animals were sacrificed at 6, 24, and 48 h, and 6 days post-SAH. Dural whole mounts were immunohistochemically reacted with antibodies to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and serotonin (5-HT). SP-like immunostaining was substantially reduced after SAH and subsequently returned to control levels at 6 days. NPY-like fiber innervation of the dura was markedly reduced after SAH; although immunostaining intensity increased, it had not returned to control levels at 6 days. The 5-HT content of dural mast cells identified by immunostaining markedly decreased at 6 and 24 h and returned to control levels at 48 h. In contrast, CGRP immunostaining was unchanged in all experimental groups. One possible explanation for this differential response is that subpopulations of trigeminovascular neurons containing SP, CGRP, or CGRP and SP respond differently to various stimuli, including SAH. Another possibility is a differential release of SP or CGRP from the same fiber. To the best of our knowledge this is the first documentation that the dura is also a target for intracranial pathological processes, such as SAH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Interaction between free radicals and excitatory amino acids in the blood-brain barrier disruption after iron injury in the rat.
Excitatory amino acids and oxygen free radicals have been reported to cooperate in the genesis of brain injury in vivo and in vitro. In this study, we tested the capacity of a noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801, and a 21-aminosteroid, U-74006F, tirilazad mesylate, to block the opening of the blood-brain barrier after subarachnoid injection of FeCl2, which is believed to cause a primarily "pure" free radical insult. Subarachnoid injection of FeCl2 resulted in a significant 10-fold increase in Evans blue extravasation while sham injection or NaCl injection had no effect. Pretreatment with either MK-801 or U-74006F significantly reduced the FeCl2-induced increase in capillary permeability by 43 and 63%, respectively (p < 0.05). Combined treatment with MK-801 and U-74006F resulted in a 65% reduction in vascular leakage that was not significantly greater than pretreatment with either drug alone. These results show that both excitatory amino acids and free radicals can damage the cerebral microvasculature and that an excitatory amino acid antagonist can partially protect the blood-brain barrier after free radical-induced injury.
Amino Acids↗
Recovery of vision after transcranial decompression of pituitary apoplexy characterized by third ventricular hemorrhage.
The authors present a case of pituitary apoplexy characterized by massive third ventricular hemorrhage. This rare complication, which caused total blindness in the patient, a 67-year-old man, was treated with transcranial decompression of the pituitary tumor and removal of a blood clot from the third ventricle. After surgery, the patient totally recovered his vision. To the best of our knowledge, this is the first case of a patient with pituitary apoplexy that ruptured into the third ventricle (diagnosed by imaging studies) who was treated by emergency transcranial decompression.
Adenoma↗
HCV infection in HBsAg positive chronic liver disease.
The prevalence of anti-HCV antibodies was determined for a group of 68 patients with various forms of chronic liver disease. All patients that were anti-HCV positive but did not show signs of HBV replication had severe liver disease. We therefore suggest that HCV may be responsible for liver damage in HBsAg positive subjects when there are no evident signs of HBV replication.
Chronic Disease↗
Postoperative venous thromboembolism and brain tumors: Part I. Clinical profile.
Forty-six patients who underwent surgery for brain tumors were studied prospectively with 125I labeled Fibrinogen leg scans to detect postoperative venous thrombosis. The incidence of thrombosis was 72% for meningioma patients, 60% for glioblastoma patients, and 20% for brain metastasis patients. Correlation between the occurrence of venous thrombosis and the various clinical factors thought to be responsible for the high incidence of thrombosis generally failed to show statistical significance. This finding, along with the marked variation in the incidence of venous thrombosis between the different brain tumor groups, strongly suggests that biological factors play a more important role than clinical factors in determining which brain tumor patient will suffer a postoperative thrombotic event.
Brain Neoplasms↗
Influence of the sympathetic nervous system as well as trigeminal sensory fibres on rat dural mast cells.
The dura mater has attracted considerable attention as an exquisitely sensitive tissue implicated as playing a role in various cephalalgias including vascular headache. Because of the potential clinical impact of the relationship/interaction of neural elements and mast cells the influence of sensory and autonomic nerve fibres on mast cells of the rat dura mater was studied. The trigeminal or superior cervical ganglion was electrically stimulated and the mast cells were examined. Wholemount supratentorial dural preparations were stained using berberine sulphate and the number of mast cells with intact vs dispersed granules counted. Unilateral stimulation of either ganglia resulted in a statistically significant increase in the percentage of mast cells with dispersed granules ipsilateral to the side of stimulation. These results support our idea that in addition to the trigeminal system the sympathetic nervous system must be considered as playing a role in the oedema pathophysiology of vascular headache.
Animals↗
Brain stem abscess treated successfully by medical therapy.
A case of a solitary brain stem abscess in a 55-year-old man is presented. The computed tomographic scan and clinical picture allowed the presumptive diagnosis to be made. The abscess resolved completely after treatment with chloramphenicol, vancomycin, and ceftazidime administered intravenously. Medical therapy should be considered as an effective treatment of a brain stem abscess, provided the antibiotic therapy is administered under close clinical and computed tomographic monitoring.
Brain Abscess↗
Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat.
A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Protective effect of a 21-aminosteroid on the blood-brain barrier following subarachnoid hemorrhage in rats.
The effects of subarachnoid injection of blood on blood-brain barrier permeability to albumin was assessed in a rat model. Subarachnoid injection of blood caused a significant sixfold increase in Evans blue extravasation, whereas sham operation or NaCl injection had no effect. In addition, subarachnoid injections of arachidonic acid or FeCl2 increased blood-brain barrier permeability to Evans blue 16- and 10-fold, respectively. The capillary permeability after subarachnoid injection of blood was normalized by pretreatment with a novel 21-aminosteroid, U-74006F, that has antioxidant and antilipolytic activity. Pretreatment with U-74006F also reduced the vascular leakage induced by subarachnoid injection of arachidonic acid or FeCl2 by 50% and 45%, respectively. We conclude that damage to membrane lipids by peroxidative and/or lipolytic processes is involved in the subarachnoid hemorrhage-induced blood-brain barrier opening and that U-74006F protects the blood-brain barrier against the effects of subarachnoid hemorrhage by preventing or limiting these pathologic membrane lipid changes.
Animals↗