scholarly journals Source and cause of endothelin-1 release to cerebrospinal fluid after subarachnoid hemorrhage

1997 ◽  
Vol 3 (4) ◽  
pp. E9
Author(s):  
Ryszard M. Pluta ◽  
Robert J. Boock ◽  
John K. Afshar ◽  
Kathleen Clouse ◽  
Mima Bacic ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Plasma Levels ◽  
Transient Cerebral Ischemia ◽  
Endothelin 1 ◽  
Delayed Cerebral Vasospasm ◽  
Ruptured Intracranial Aneurysm

Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 μM), methemoglobin (10 μM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 ± 2.2 pg/ml and ET-1 plasma levels were 1.2 ± 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 ± 1.7 pg/ml in CSF and 2.7 ± 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 ± 0.4 pg/ml at the occlusion vs. 3.1 ± 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 ± 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 ± 0.8 pg/ml vs. 0.1 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 ± 0.6 pg/ml vs. 0 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 ± 0.6 vs. 6.4 ± 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.

Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage

1997 ◽  
Vol 87 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Ryszard M. Pluta ◽  
Robert J. Boock ◽  
John K. Afshar ◽  
Kathleen Clouse ◽  
Mima Bacic ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Vasospasm ◽  
Plasma Levels ◽  
Transient Cerebral Ischemia ◽  
Content Type ◽  
Endothelin 1 ◽  
Fine Print

✓ Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 µM), methemoglobin (10 µM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 ± 2.2 pg/ml and ET-1 plasma levels were 1.2 ± 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 ± 1.7 pg/ml in CSF and 2.7 ± 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 ± 0.4 pg/ml at the occlusion vs. 3.1 ± 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 ± 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 ± 0.8 pg/ml vs. 0.1 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 ± 0.6 pg/ml vs. 0 ± 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 ± 0.6 vs. 6.4 ± 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.

Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage

2005 ◽  
Vol 64 ◽  
pp. S2-S5 ◽  
Author(s):  
Iruena Moraes Kessler ◽  
Yolanda Galindo Pacheco ◽  
Silene Paulino Lozzi ◽  
Antônio Santos de Araújo ◽  
Franz Jooji Onishi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Endothelin 1

scholarly journals Endothelin-1 concentration increases in the cerebrospinal fluid in cerebral vasospasm caused by subarachnoid hemorrhage

2000 ◽  
Vol 53 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Kensuke Suzuki ◽  
Kotoo Meguro ◽  
Takeshi Sakurai ◽  
Yoshifumi Saitoh ◽  
Sadayuki Takeuchi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Endothelin 1

Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: The relationship to endothelin-1 levels in the cerebrospinal fluid

Life Sciences ◽  
1991 ◽  
Vol 49 (11) ◽  
pp. 841-848 ◽  
Author(s):  
Yasuo Matsumura ◽  
Ruriko Ikegawa ◽  
Yasunori Suzuki ◽  
Masanori Takaoka ◽  
Takeshi Uchida ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Endothelin 1 ◽  
The Relationship

Endothelin-1 Gene Polymorphisms Influence Cerebrospinal Fluid Endothelin-1 Levels Following Aneurysmal Subarachnoid Hemorrhage

2014 ◽  
Vol 17 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Matthew J. Gallek ◽  
Sheila A. Alexander ◽  
Elizabeth Crago ◽  
Paula R. Sherwood ◽  
Megan Klamerus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Exposure Rate ◽  
Positive Group ◽  
Endothelin 1 ◽  
Protein Levels ◽  
Angiographic Vasospasm

Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm. Specifically, this study evaluated the differences between variant positive and variant negative groups of nine different ET-1 single-nucleotide polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One functional SNP and eight ET-1 tagging SNPs were selected because they represent genetic variability in the entire ET-1 gene. The variant negative group of SNP rs2070699 was associated with a significantly higher ET-1 exposure rate than the variant positive group ( p = 0.004), while the variant positive group of the rs5370 group showed a trend toward association with a higher ET-1 exposure rate ( p = 0.051). Other SNPs were not informative. This is the first study to show differences in ET-1 exposure rate 72 hr before angiography in relation to ET-1 genotypes. These exploratory findings need to be replicated in a larger study; if replicated, these differences in genotypes may be a way to inform clinicians of those patients at a higher risk of increased ET-1 protein levels, which may lead to a higher risk of angiographic vasospasm.

Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

2007 ◽  
Vol 107 (5) ◽  
pp. 945-950 ◽  
Author(s):  
Carla S. Jung ◽  
Edward H. Oldfield ◽  
Judith Harvey-White ◽  
Michael G. Espey ◽  
Michael Zimmermann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Control Group ◽  
Type I ◽  
Endogenous Inhibitor ◽  
Primate Model ◽  
Delayed Cerebral Vasospasm

Object Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be evoked by the decreased availability of nitric oxide (NO). Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of NO synthase (NOS), have been associated with the course and degree of cerebral vasospasm in a primate model of SAH. In this study, the authors sought to determine if similar changes in CSF ADMA levels are observed in patients with SAH, and whether these changes are associated with NO and NOS metabolite levels in the CSF and the presence of cerebral vasospasm. Methods Asymmetric dimethyl-l-arginine, l-arginine, l-citrulline, and nitrite levels were measured in CSF and serum samples collected during the 21-day period after a single aneurysmal SAH in 18 consecutive patients. Samples were also obtained in a control group consisting of seven patients with Chiari malformation Type I and five patients with spontaneous intracerebral hemorrhage without SAH. Vasospasm, defined as a greater than 11% reduction in the anterior circulation vessel diameter ratio compared with the ratio calculated from the initial arteriogram, was assessed on cerebral arteriography performed around Day 7. Results In 13 patients with SAH, arteriographic cerebral vasospasm developed. Cerebrospinal fluid ADMA levels in patients with SAH were higher than in those in the control group (p < 0.001). The CSF ADMA level remained unchanged in the five patients with SAH without vasospasm, but was significantly increased in patients with vasospasm after Day 3 (6.2 ± 1.7 μM) peaking during Days 7 through 9 (13.3 ± 6.7 μM; p < 0.001) and then gradually decreasing between Days 12 and 21 (8.8 ± 3.2 μM; p < 0.05). Nitrite levels in the CSF were lower in patients with vasospasm compared to patients without vasospasm (p < 0.03). Cerebrospinal fluid ADMA levels positively correlated with the degree of vasospasm (correlation coefficient [CC] = 0.88, p = 0.0001; 95% confidence interval [CI] 0.74–0.95) and negatively correlated with CSF nitrite levels (CC = −0.55; p = 0.017; 95% CI −0.81 to −0.12). Conclusions These results support the hypothesis that ADMA is involved in the progression of cerebral vasospasm. Asymmetric dimethyl-l-arginine and its metabolizing enzymes may be a future target for treatment of cerebral vasospasm after SAH.

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