Accelerated Non-Muscle Contraction after Subarachnoid Hemorrhage: Cerebrospinal Fluid Testing in a Culture Model

Neurosurgery ◽  
1990 ◽  
Vol 27 (6) ◽  
pp. 921-928 ◽  
Author(s):  
Yoshihiro Yamamoto ◽  
David H. Bernanke ◽  
Robert R. Smith
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Collagen Matrix ◽  
Aneurysm Rupture ◽  
Lattice Contraction ◽  
Symptomatic Vasospasm ◽  
Luminal Narrowing ◽  
Chronic Vasospasm ◽  
Vitro Model

Abstract The cause of chronic cerebral vasospasm after subarachnoid hemorrhage has been studied intensively, but it is still controversial whether the observable luminal narrowing should be attributed to the contraction of vascular smooth muscle cells or whether it results from some organic change in the wall. A proliferation of myointimal cells, accompanied by increased deposition of collagen, as well as myonecrosis, have been frequently observed several days after aneurysm rupture. Studies from our laboratory showed that these myointimal cells had characteristics identical to myofibroblasts. In this study, we quantitatively and morphologically examined the effect of cerebrospinal fluid on the ability of myofibroblasts to alter collagen matrices using an in vitro model. Myofibroblasts contract the collagen matrix by rearranging or compacting the framework of collagen fibers. Cerebrospinal fluid obtained from patients with recently ruptured aneurysms significantly accelerated lattice contraction, especially when the patient developed symptomatic vasospasm. This study suggests that myofibroblasts in the spastic artery can produce a contractile force that contributes to chronic vasospasm, tightening the proliferated collagen. Some unknown agent present in bloody cerebrospinal fluid accelerates the rearrangement of the collagen lattice by myofibroblasts, both of which have, until now, been considered non-contractile components.

Effect of the 21-aminosteroid U-74006F on cerebral vasospasm following subarachnoid hemorrhage

1989 ◽  
Vol 71 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Mario Zuccarello ◽  
Jeffery T. Marsch ◽  
Gerald Schmitt ◽  
James Woodward ◽  
Douglas K. Anderson
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Autologous Blood ◽  
Contrast Material ◽  
Rabbit Model ◽  
Membrane Lipid ◽  
Basilar Arteries ◽  
Flow Through ◽  
Chronic Vasospasm

✓ The purpose of this study was to use a new 21-aminosteroid (U-74006F) with in vitro antioxidant and antilipolytic properties as a pharmacological probe to assess the role of lipid hydrolysis and peroxidation in a rabbit model of subarachnoid hemorrhage (SAH)-induced vasospasm. Cerebral angiograms were performed on 15 rabbits. Eighteen hours later, 1 cc/kg of autologous blood was infused into the cisterna magna of all 15 animals. Six rabbits received no treatment, six received U-74006F starting 30 minutes after SAH, and three rabbits received the vehicle for U-74006F starting 30 minutes after SAH. At 72 hours post-SAH, a second angiogram was obtained. Digital subtraction angiographic techniques were used to measure the diameter of and contrast material flow through the basilar artery. At 72 hours post-SAH, vasospasm was evident in all untreated and vehicle-treated rabbits. The diameter of and the flow through the basilar artery were significantly reduced 42.3% ± 6.6% and 46.8% ± 5.8%, respectively, below pre-SAH levels (means ± standard error of the means). Treatment with U-74006F eliminated the SAH-induced vasospasm; in treated animals, both the flow through and the diameter of the basilar arteries were at pre-SAH levels. These findings indicate that: 1) membrane lipid changes (that is, hydrolysis with eicosanoid production and/or peroxidation) contribute to the chronic vasospasm resulting from SAH, and 2) U-74006F prevents the SAH-induced chronic vasospasm in this model by limiting these pathological membrane events.

Alterations of mechanical properties in canine basilar arteries after subarachnoid hemorrhage

1989 ◽  
Vol 71 (3) ◽  
pp. 430-436 ◽  
Author(s):  
Phyo Kim ◽  
Thoralf M. Sundt ◽  
Paul M. Vanhoutte
Keyword(s):  
Mechanical Properties ◽  
Subarachnoid Hemorrhage ◽  
Autologous Blood ◽  
Myogenic Tone ◽  
Control Group ◽  
Resting Tension ◽  
Length Contraction ◽  
Basilar Arteries ◽  
Chronic Vasospasm

✓ The purpose of this study was to examine the hypotheses that structural stiffening of the arterial wall contributes to chronic cerebral vasospasm, and that alteration in properties of smooth muscle takes place after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage and subsequent chronic vasospasm were induced in dogs by two cisternal injections of autologous blood (on Day 0 and Day 2). Vasospasm was confirmed by angiography performed on Day 0 and Day 7. Animals in the control group underwent angiography only. On Day 8, the mechanical properties of the basilar arteries were studied in vitro. Passive compliance, measured under total inhibition of spontaneous myogenic tone with diltiazem (10−4 M) plus papaverine (10−4 M) was smaller in the SAH group. The length-contraction curve was shifted to the left and the optimum length for maximum contraction (Lmax) was significantly shorter in the spastic blood vessels. The spontaneous myogenic tone was augmented in the SAH group, resulting in an increase in resting tension at each length. By contrast, the maximum contractions in response to KCl and uridine 5′-triphosphate were markedly reduced in the SAH group, without changes in sensitivity to these agents. These differences in mechanical properties were observed in rings both with and without endothelium. The results indicate that, in chronic vasospasm, stiffening of the noncontractile component of the vasculature takes place as well as alterations in the contractile component, both of which presumably contribute to the shift in resting length-tension relationship and length-contraction relationship of the artery. The decreased distensibility, the increase in resting tension, and the shortening of the Lmax all favor a smaller diameter of the artery after SAH, possibly contributing to vasospasm.

CSF leukotriene C4 following subarachnoid hemorrhage

1988 ◽  
Vol 69 (4) ◽  
pp. 488-493 ◽  
Author(s):  
Pietro Paoletti ◽  
Paolo Gaetani ◽  
Guido Grignani ◽  
Lucia Pacchiarini ◽  
Vittorio Silvani ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Subarachnoid Hemorrhage ◽  
Arterial Spasm ◽  
Lipoxygenase Pathway ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Csf Levels ◽  
Fine Print

✓ Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p < 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p < 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.

scholarly journals Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury

2021 ◽  
pp. 0271678X2110206
Author(s):  
Kevin Akeret ◽  
Raphael M Buzzi ◽  
Christian A Schaer ◽  
Bart R Thomson ◽  
Florence Vallelian ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Ex Vivo ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Unmet Need ◽  
Aneurysm Rupture ◽  
Secondary Brain Injury ◽  
Oxidative Potential ◽  
Macrophage Response

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.

scholarly journals In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices.

1983 ◽  
Vol 97 (5) ◽  
pp. 1648-1652 ◽  
Author(s):  
R Montesano ◽  
L Orci ◽  
P Vassalli
Keyword(s):  
Endothelial Cells ◽  
Three Dimensional ◽  
Collagen Matrix ◽  
Collagen Gels ◽  
Collagen Matrices ◽  
Narrow Lumen ◽  
Capillary Endothelial Cells ◽  
Vitro Model

We have studied the behavior of cloned capillary endothelial cells grown inside a three dimensional collagen matrix. Cell monolayers established on the surface of collagen gels were covered with a second layer of collagen. This induced the monolayers of endothelial cells to reorganize into a network of branching and anastomosing capillary-like tubes. As seen by electron microscopy, the tubes were formed by at least two cells (in transverse sections) delimiting a narrow lumen. In addition, distinct basal lamina material was present between the abluminal face of the endothelial cells and the collagen matrix. These results showed that capillary endothelial cells have the capacity to form vessel-like structures with well-oriented cell polarity in vitro. They also suggest that an appropriate topological relationship of endothelial cells with collagen matrices, similar to that occurring in vivo, has an inducive role on the expression of this potential. This culture system provides a simple in vitro model for studying the factors involved in the formation of new blood vessels (angiogenesis).

Plasma Platelet-Activating Factor–Acetyl Hydrolase Activity and the Levels of Free Forms of Biomarker of Lipid Peroxidation in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2011 ◽  
Vol 70 (3) ◽  
pp. 602-609 ◽  
Author(s):  
Yutaka Hirashima ◽  
Masaru Doshi ◽  
Nakamasa Hayashi ◽  
Shunro Endo ◽  
Yoko Akazawa ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Acyl Chain ◽  
Platelet Activating Factor ◽  
Prostaglandin F2α ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Symptomatic Vasospasm

Abstract Background: Free radicals and lipid peroxidation are thought to be related to the vasospasm generation after subarachnoid hemorrhage (SAH). Plasma platelet-activating factor-acetyl hydrolase (PAF-AH) degrades phospholipids with an oxidatively modified fatty acyl chain. Objective: To compare plasma PAF-AH activity and free forms of biomarker of lipid peroxidation in cerebrospinal fluid (CSF) between patients with and without symptomatic vasospasm (SVS) after SAH. Methods: The identification of PAF-AH in CSF was performed by Western blotting. The genotype at position 279 of the plasma PAF-AH gene was determined. The activities of PAF-AH and the levels of free 8-iso-prostaglandin F2α (free isoPs), free hydroxyoctadecadienoic acid (free HODE), and free hydroxyeicosatetraenoic acid (free HETE) in CSF were measured. Results: The PAF-AH in CSF was confirmed to be only the plasma type. The genotype of the plasma PAF-AH was not different between patients with and without SVS. Free isoPs, free HODE, and free HETE showed higher values in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The PAF-AH activity also was higher in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The associations between PAF-AH activity and free isoPs, and between PAF-AH activity and free HODE were significant. Conclusion: Oxidized lipids of lipoproteins and blood cell membranes produced by reactive oxygen species in CSF when SAH occurs may be the main source of lipid peroxidation. Plasma PAF-AH can hydrolyze oxidized phospholipids, and may attenuate the spreading of lipid peroxidation and participate in defense mechanisms against vasospasm after SAH.

Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage

2006 ◽  
Vol 105 (5) ◽  
pp. 723-729 ◽  
Author(s):  
Martina Stippler ◽  
Elizabeth Crago ◽  
Elad I. Levy ◽  
Mary E. Kerr ◽  
Howard Yonas ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Doppler Ultrasonography ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Treated Group ◽  
Aneurysm Rupture ◽  
Current Standard ◽  
Ruptured Aneurysms ◽  
Symptomatic Vasospasm ◽  
Fisher Grade ◽  
Significant Difference

Object Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis. Methods Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4 infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration. Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4-treated group. Conclusions Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.

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