Cerebral arterial pathology in experimental subarachnoid hemorrhage

1983 ◽  
Vol 58 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Tetsumori Yamashima ◽  
Shinjiro Yamamoto
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Smooth Muscle Cells ◽  
Morphological Changes ◽  
Autologous Blood ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Internal Elastic Lamina ◽  
Content Type ◽  
Fine Print

✓ Pathological changes of the cerebral arteries were studied in 30 dogs after subarachnoid injections of saline, fresh autologous blood, epinephrine, blood plus epinephrine, norepinephrine, or blood plus norepinephrine. Macroscopically, the circle of Willis was maximally dilated after the injection of epinephrine and was constricted following administration of blood plus epinephrine. Microscopically, neither saline nor blood produced abnormalities, except for minor changes of the adventitia in the latter. Epinephrine produced frank necrosis of smooth-muscle cells, which was subsequently replaced by fibrosis in the media of larger subarachnoid arteries, and the leakage of necrotic material from the infarcted hypothalamus contributed to these lesions. Blood plus epinephrine produced marked changes in the internal elastic lamina and tortuosities of the nuclei of smooth-muscle cells, while norepinephrine and blood plus norepinephrine produced only minor changes. Previously reported findings of morphological changes due to vasospasm after subarachnoid hemorrhage were confirmed experimentally, but such changes were found only after application of epinephrine. It is suggested that epinephrine produced the most severe vasospasm among the five substances tested.

The effect of hemoglobin and its metabolites on energy metabolism in cultured cerebrovascular smooth-muscle cells

1995 ◽  
Vol 82 (2) ◽  
pp. 244-249 ◽  
Author(s):  
Kazuhiko Nagatani ◽  
Jeffery E. Masciopinto ◽  
Peter B. Letarte ◽  
Robert A. Haworth ◽  
Thomas A. Duff
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Energy Levels ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Inhibitory Effect ◽  
Intact Cells ◽  
Content Type ◽  
Cerebrovascular Smooth Muscle Cells ◽  
Fine Print

✓ Cerebral arteries in spasm have been found to contain low levels of adenosine triphosphate (ATP), and it has been postulated that this change in levels results from hypoxia produced by arterial encasement in clotted material. This study was undertaken to determine whether any of four blood-derived agents, ferrous hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy levels in cerebral artery smooth-muscle cells. Twenty-four-hour exposure of cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with electron transport and with creatine phosphokinase activity in intact cells; however, bilirubin showed no inhibitory effect on this enzyme in cell-free conditions. The findings indicate that hemoglobin and bilirubin may be responsible for diminished energy levels in cerebral arteries. These observations also suggest that bilirubin may exert its effect on ATP by impairing mitochondrial function.

Effect of hypoxia on the contractile response to KCl, prostaglandin F2α, and hemoglobin

1987 ◽  
Vol 67 (4) ◽  
pp. 565-572 ◽  
Author(s):  
Tadayoshi Nakagomi ◽  
Neal F. Kassell ◽  
Tomio Sasaki ◽  
Shigeru Fujiwara ◽  
R. Michael Lehman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Contractile Response ◽  
Direct Action ◽  
Cerebral Arteries ◽  
Prostaglandin F2α ◽  
Muscle Cells ◽  
Content Type ◽  
Fine Print

✓ The purpose of this experiment was to evaluate the effect of hypoxia on the in vitro contractile responses of canine basilar artery to KCl, prostaglandin (PG) F2α, and hemoglobin. Hypoxia was induced by changing the bubbling gas mixture in the chamber from 95% O2/5% CO2 to 95% N2/5% CO2. Hypoxia augmented the contractile response developed at 95% O2 to 25 mM and 50 mM KCl, 3 × 10−7 M and 10−5 M PGF2α, and 10−6 M hemoglobin. No significant alteration of the hypoxic augmentation in any preparation exposed to 25 mM KCl, 3 × 10−7 M PGF2α, or 10−6 M hemoglobin was observed with guanethidine (10−5 M), prazosin (10−5 M), methysergide (10−5 M), or diphenhydramine (10−5 M). Endothelial denudation did not affect hypoxic augmentation. Hypoxia did not cause any alteration of the contractile response to 10−6 M PGF2α in Ca++-free media. Pretreatment with a calcium channel blocker, nicardipine, significantly inhibited the hypoxic potentiation of the contractile response to 25 mM KCl, 3 × 10−7 M PGF2α, and 10−6 M hemoglobin. These results suggest that hypoxia augments the contractile response to these agonists by a direct action on the smooth-muscle cells, facilitating the transmembrane influx of extracellular calcium. Hypoxia of smooth-muscle cells in the major cerebral arteries might be involved in the pathogenesis of vasospasm.

Subarachnoid hemorrhage and cerebrovascular spasm

1981 ◽  
Vol 55 (6) ◽  
pp. 869-876 ◽  
Author(s):  
O. Petter Eldevik ◽  
Kristian Kristiansen ◽  
Ansgar Torvik
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Morphological Changes ◽  
Autologous Blood ◽  
Cerebral Arteries ◽  
Light And Electron Microscopy ◽  
Brain Vessels ◽  
Content Type ◽  
Perfusion Fixation ◽  
The Brain ◽  
Fine Print

✓ Artificial subarachnoid hemorrhage (SAH) produced by injection of autologous blood into the cisterna magna in dogs gave rise to considerable narrowing or spasm of the basilar artery and its branches, including the posterior cerebral arteries, as demonstrated by cerebral angiography. Repeated cisternal injections of blood at various intervals produced more severe spasm than a single injection. After perfusion-fixation of the brain, the cerebral arteries were examined by light and electron microscopy. None of the animals showed abnormalities in the intima or media of the vessel walls. Previously reported findings of morphological changes due to spasm could not be confirmed. Postmortem examination of brain vessels from nine patients with SAH and arterial spasm showed no specific changes that could be ascribed to spasm.

An Arteriovenous Malformation Model for Stereotactic Radiosurgery Research

Neurosurgery ◽  
2007 ◽  
Vol 61 (1) ◽  
pp. 152-159 ◽  
Author(s):  
Reza Jahan ◽  
Timothy D. Solberg ◽  
Daniel Lee ◽  
Paul Medin ◽  
Satoshi Tateshima ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Arteriovenous Malformation ◽  
Smooth Muscle Cells ◽  
Stereotactic Radiosurgery ◽  
Intimal Hyperplasia ◽  
Morphological Changes ◽  
Muscle Cells ◽  
Collagen Type Iv ◽  
Internal Elastic Lamina ◽  
Type Iv

Abstract OBJECTIVE To introduce the utilization of a swine arteriovenous malformation (AVM) model for stereotactic radiosurgery research and to describe the morphological changes in the vessels after radiation. METHODS The model was created in six animals by creation of a right-sided carotid-jugular fistula. Pre- and postsurgical hemodynamic evaluation was performed. The left rete was radiated in four animals; two animals were not radiated. All animals were sacrificed 4 months after surgery, and the bilateral retia were obtained at autopsy. RESULTS There were no procedure-related complications. A pressure gradient of 20 mmHg across the nidus was obtained after surgery. The peak velocity in the arterial feeder increased from 18.5 to 83 cm/s. Microscopic examination of the control animals showed intimal hyperplasia and disrupted internal elastic lamina, similar to human AVMs. The radiated retia showed more prominent intimal hyperplasia. This was confirmed by histometric studies showing greater luminal occlusion in radiated specimens. Adventitial fibrosis was prominent in the radiated retia and was absent in the control animals. Immunohistochemical studies showed proliferating smooth muscle cells in the intima. The adventitial fibrosis consisted of smooth muscle cells surrounded by collagen Type IV extracellular matrix. CONCLUSION The nidus component and high-flow vasculopathy make this an attractive model for stereotactic radiosurgery research. Histology of the radiated models is similar to those described in radiated human AVMs. Further studies of the model are warranted to gain a better understanding of the cellular and molecular events in AVM vessels after stereotactic radiosurgery.

Immediate early gene expression in vascular smooth-muscle cells synergistically induced by hemolysate components

1999 ◽  
Vol 90 (6) ◽  
pp. 1083-1090 ◽  
Author(s):  
Xiaoyu Wang ◽  
Linda S. Marton ◽  
Bryce K. A. Weir ◽  
R. Loch Macdonald
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Synergistic Effects ◽  
Muscle Cells ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Content Type ◽  
Fine Print

Object. Vasospasm after subarachnoid hemorrhage is associated with changes in modulators of vascular tone in the arterial wall and is related to the presence of erythrocyte hemolysate in the subarachnoid space. The purpose of this study was to determine the compounds in erythrocyte hemolysate that are responsible for changing smooth-muscle cell gene expression.Methods. Rat aorta smooth-muscle cells were exposed to erythrocyte hemolysate in vitro and the effects on immediate early gene messenger (m)RNA levels were determined by competitive reverse transcriptase—polymerase chain reaction.Message levels for c-fos, jun B, and c-jun were increased in the presence of hemolysate, reaching maximum expression between 30 and 60 minutes, whereas the level of jun D mRNA was unaffected. Increasing doses of hemolysate caused greater expression of c-fos and jun B, but not c-jun. Adenosine triphosphate and hemoglobin, possible spasmogens present in hemolysate, caused much smaller and more rapid increases in c-fos expression than whole hemolysate. Size fractionation showed that all of the c-fos mRNA—inducing activity of hemolysate was recovered with molecules greater than 6 kD. Following separation of hemolysate proteins by hydrophobic interaction chromatography, only one of the three fractions had partial activity. Recombining the three fractions, however, yielded greater c-fos activation than any combination of two.Conclusions. Multiple high-molecular-weight components present in erythrocytes have synergistic effects on gene expression in smooth-muscle cells. The differences in patterns of gene induction suggest that multiple signaling pathways are activated.

Intracellular mechanisms involved in the responses of cerebrovascular smooth-muscle cells to hemoglobin

1994 ◽  
Vol 80 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Bozena A. M. Vollrath ◽  
Bryce K. A. Weir ◽  
R. Loch Macdonald ◽  
David A. Cook
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Phospholipase C ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Inositol Triphosphate ◽  
Content Type ◽  
Transient Nature ◽  
Cerebrovascular Smooth Muscle Cells

✓ An investigation was undertaken of the mechanism by which oxyhemoglobin and its analog methemoglobin might cause cerebrovascular spasm. The effect of these compounds on the levels of intracellular inositol triphosphate and calcium in cultured primate cerebrovascular smooth-muscle cells and the contractile action of oxyhemoglobin on isolated rings of primate cerebral arteries were also examined. Oxyhemoglobin, but not methemoglobin, produces a transient but highly significant increase in the intracellular levels of inositol triphosphate. Intracellular calcium levels in these cells are increased by thrombin, aluminum tetrafluoride, and oxyhemoglobin, and the sustained elevation in intracellular calcium is prevented by ethyleneglycol tetra-acetic acid and the phospholipase C inhibitor neomycin. Removal of the oxyhemoglobin after as long as 48 hours' incubation with this compound allowed cells to rapidly reduce their intracellular calcium levels to near normal. Oxyhemoglobin produced contractions of isolated rings of both normal and spastic cerebral arteries, although the response of spastic vessels was significantly smaller. This effect was inhibited by neomycin. The addition of neomycin relaxed arteries that were contracted with oxyhemoglobin, 5-hydroxytryptamine, or potassium chloride. It is thus likely that activation of phospholipase C is a critical step in the development of vasospasm, but the transient nature of the response to inositol triphosphate suggests that the sustained contraction may arise from other phospholipase C-dependent mechanisms.

Role of protein tyrosine phosphorylation in erythrocyte lysate—induced intracellular free calcium concentration elevation in cerebral smooth-muscle cells

1999 ◽  
Vol 90 (4) ◽  
pp. 743-751 ◽  
Author(s):  
Satoshi Iwabuchi ◽  
Linda S. Marton ◽  
John H. Zhang
Keyword(s):  
Molecular Weight ◽  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Smooth Muscle Cells ◽  
Tyrosine Phosphorylation ◽  
Kinase Inhibitors ◽  
Weight Fraction ◽  
Muscle Cells ◽  
Content Type ◽  
Fine Print

Object. Tyrosine kinases play an important role in the regulation of systemic vascular smooth-muscle tone. The authors studied the involvement of protein tyrosine kinase activity in erythrocyte lysate—mediated signal transduction in cerebral smooth-muscle cells.Methods. Tyrosine kinase phosphorylation and intracellular free Ca++ ([Ca++]i) were measured in rat aortic and basilar artery smooth-muscle cells by using Western blot and fura 2-acetoxymethyl ester microfluorimetry. Erythrocyte lysate enhanced tyrosine phosphorylation in cultured rat aortic and basilar smooth-muscle cells and induced a rapid transient and a prolonged plateau phase of [Ca++]i response in rat basilar smooth-muscle cells. The tyrosine kinase inhibitors genistein and tyrphostin A51 (administered at concentrations of 30 or 100 µM) attenuated both phases of erythrocyte lysate—induced [Ca++]i elevation. Erythrocyte lysate was separated into low- (< 10 kD, which contains adenine nucleotides) and high- (> 10 kD, which contains hemoglobin) molecular-weight fractions; these fractions were tested separately in these cells. The low-molecular-weight fraction produced a similar [Ca++]i response to that of erythrocyte lysate and the high-molecular-weight fraction produced a small response. The [Ca++]i responses from both fractions were inhibited by tyrosine kinase inhibitors.Conclusions. To the authors' knowledge, this is the first report to show that tyrosine phosphorylation may be involved in erythrocyte lysate—induced signal transduction and [Ca++]i responses in cerebral smooth-muscle cells.

Presence of smooth-muscle cells in the subdural neomembrane

1981 ◽  
Vol 54 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Nobuyuki Kawano ◽  
Kinuko Suzuki
Keyword(s):  
Electron Microscopy ◽  
Smooth Muscle ◽  
Light Microscopy ◽  
Smooth Muscle Cells ◽  
Subdural Hematoma ◽  
Light And Electron Microscopy ◽  
Chronic Subdural Hematoma ◽  
Muscle Cells ◽  
Content Type ◽  
Fine Print

✓ The authors encountered a case of chronic subdural hematoma of which the subdural neomembrane (SN) showed numerous spindle-shaped cells identified as smooth-muscle cells (SMC's) by electron microscopy. On reexamination of 214 cases from the files, SMC's were found with light microscopy in seven cases. In these cases, the SN was well organized (collagenized). In three additional cases examined with both light and electron microscopy, SMC's were not apparent with light microscopy. However, in all cases, cells with ultrastructural features of both fibroblasts and SMC's were observed. Well formed SMC's were found in two additional cases of well organized membrane. Based on these observations, it is concluded that the presence of SMC's in the SN is not a rare phenomenon. The possible origin of SMC's in the SN and their pathological significance to the organizing process of chronic subdural hematoma are discussed.

Glutathione monoethyl ester and inhibition of the oxyhemoglobin-induced increase in cytosolic calcium in cultured smooth-muscle cells

1999 ◽  
Vol 90 (3) ◽  
pp. 527-532 ◽  
Author(s):  
Takashi Arai ◽  
Naoshi Takeyama ◽  
Takaya Tanaka
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Muscle Cells ◽  
Cytosolic Calcium ◽  
Acetoxymethyl Ester ◽  
Content Type ◽  
Transient Elevation ◽  
Fine Print

Object. The mechanism of arterial vasoconstriction caused by oxyhemoglobin production after subarachnoid hemorrhage was investigated.Methods. Using a fluorescent Ca++ indicator (fura-2 acetoxymethyl ester), the change in the cytosolic intracellular Ca++ concentration, [Ca++]i, was measured in cultured rat vascular smooth-muscle cells exposed to oxyhemoglobin and other substances. Oxyhemoglobin induced transient elevation of smooth-muscle cell [Ca++]i in either the presence or absence of ethyleneglycol-bis (β-aminoethylether)-N,N′-tetraacetic acid, indicating that Ca++ released by oxyhemoglobin was derived from [Ca++]i stores. In contrast, methemoglobin had no effect on the smooth-muscle cells. Exposure of the cells to reactive oxygen species generated by xanthine plus xanthine oxidase yielded the same results as with oxyhemoglobin, that is, transient elevation of smooth-muscle cell [Ca++]i. Procaine (a Ca++ channel blocker) failed to inhibit the oxyhemoglobin-induced elevation of [Ca++]i. Ryanodine (a Ca++ channel opener) plus oxyhemoglobin caused markedly greater elevation of [Ca++]i than ryanodine alone, whereas thapsigargin (an adenosine triphosphate [ATP]-dependent Ca++ pump inhibitor) plus oxyhemoglobin had no additional effect when compared with thapsigargin alone. The oxyhemoglobin-induced elevation of [Ca++]i could be blocked by an Fe++ chelator (ferene), but not by an Fe+++ chelator (deferoxamine mesylate). Treatment with either dithiothreitol or glutathione monoethyl ester markedly inhibited the oxyhemoglobin-induced elevation of [Ca++]i.Conclusions. These results indicate that Fe++-catalyzed hydroxyl radicals generated from oxyhemoglobin-derived free radicals induce the elevation of [Ca++]i by inhibiting the ATP-dependent Ca++ pump rather than the Ca++ channels in the sarcoplasmic reticulum and that thiols may prevent Ca++ pump inactivation by inhibiting the oxidation of membrane sulfhydryl groups.

Experimental vasospasm in cultured arterial smooth-muscle cells

1988 ◽  
Vol 69 (1) ◽  
pp. 92-97 ◽  
Author(s):  
Satoshi Fujii ◽  
Kazuhiko Fujitsu
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ultrastructural Changes ◽  
Vasoactive Agents ◽  
Arterial Smooth Muscle ◽  
Content Type ◽  
Aortic Media ◽  
Arterial Smooth Muscle Cells ◽  
Fine Print

✓ Smooth-muscle cells were cultured from rat aortic media, then oxyhemoglobin and other agents including serotonin, norepinephrine, and angiotensin II were added separately to the medium. Contractile and ultrastructural changes of the cells were examined with electron microscopy during the first 2 weeks of incubation. Oxyhemoglobin not only produced progressive contraction of the arterial smooth-muscle cells, but it also caused ultrastructural changes that resembled myonecrosis. In contrast, there was no evidence of progressive contraction or ultrastructural changes either in control cultures or in cultures with the other vasoactive agents. Although washout of oxyhemoglobin 3 hours after administration prevented continued contraction of the cells, washout 24 hours or longer after administration had no preventive effect. Judging from these results and from the fact that the culture medium was changed every 2 days, it is unlikely that accumulation of exogenous vasoactive agents caused these changes. The contraction and suggestive myonecrosis of the arterial smooth-muscle cells are probably caused by some intrinsic process initiated by oxyhemoglobin. The culture of cerebral arterial smooth-muscle cells requires further technical improvement; nevertheless, these results obtained with the smooth-muscle cells of rat aortic media indicate that arterial smooth-muscle cells in culture provide a promising new experimental model for chronic in vitro study of cerebral arterial spasm. It is suggested from these results that cerebral arteries are particularly prone to vasospasm because of structural differences as compared to noncerebral arteries.

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