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 ◽  
...  

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.

2005 ◽  
Vol 64 ◽  
pp. S2-S5 ◽  
Author(s):  
Iruena Moraes Kessler ◽  
Yolanda Galindo Pacheco ◽  
Silene Paulino Lozzi ◽  
Antônio Santos de Araújo ◽  
Franz Jooji Onishi ◽  
...  

2000 ◽  
Vol 53 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Kensuke Suzuki ◽  
Kotoo Meguro ◽  
Takeshi Sakurai ◽  
Yoshifumi Saitoh ◽  
Sadayuki Takeuchi ◽  
...  

Life Sciences ◽  
1991 ◽  
Vol 49 (11) ◽  
pp. 841-848 ◽  
Author(s):  
Yasuo Matsumura ◽  
Ruriko Ikegawa ◽  
Yasunori Suzuki ◽  
Masanori Takaoka ◽  
Takeshi Uchida ◽  
...  

2011 ◽  
Vol 23 (4) ◽  
pp. 310-317 ◽  
Author(s):  
Hidenori Suzuki ◽  
Kenji Kanamaru ◽  
Masato Shiba ◽  
Masashi Fujimoto ◽  
Kyoko Imanaka-Yoshida ◽  
...  

1997 ◽  
Vol 87 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Ryszard M. Pluta ◽  
Robert J. Boock ◽  
John K. Afshar ◽  
Kathleen Clouse ◽  
Mima Bacic ◽  
...  

✓ 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.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jan Martin ◽  
Eva Plank ◽  
Bernhard Ulm ◽  
Jens Gempt ◽  
Maria Wostrack ◽  
...  

Abstract Background The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum. Results Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2. Conclusions In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.


Neurosurgery ◽  
2007 ◽  
Vol 60 (4) ◽  
pp. 674-680 ◽  
Author(s):  
Tibet Kacira ◽  
Rahsan Kemerdere ◽  
Pinar Atukeren ◽  
Hakan Hanimoglu ◽  
Galip Zihni Sanus ◽  
...  

Abstract OBJECTIVE The purpose of this study is to explore whether or not the levels of caspase-3 (Casp3), neuron-specific enolase (NSE), and high-sensitivity C-reactive protein (hsCRP) were elevated in cerebrospinal fluid (CSF) and serum of patients after aneurysmal subarachnoid hemorrhage (SAH). METHODS This prospective clinical study consisted of 20 patients who experienced recent aneurysmal SAH and 15 control patients who experienced hydrocephalus without any other central nervous system disease. CSF and serum samples obtained within the first 3 days, and on the fifth and seventh days of SAH were assayed for Casp3, NSE, and hsCRP by using enzyme-linked immunosorbent assay. RESULTS Levels of Casp3, NSE, and hsCRP in the CSF (P = 0.00001, P = 0.00001, and P &lt;0.003, respectively) and in the serum (P = 0.00001, P &lt;0.01, and P = 0.00001, respectively) of SAH patients were found to be elevated when compared with controls with normal pressure hydrocephalus. CONCLUSION The authors have demonstrated the synchronized elevation of Casp3, NSE, and hsCRP in both CSF and serum of patients with aneurysmal SAH. Further studies with a large number of patients are recommended to more accurately determine the roles of these molecules in aneurysmal SAH.


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