A non-enzymatic derived arachidonyl peroxide, 8-iso-prostaglandin F2α, in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage participates in the pathogenesis of 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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Increased levels of lipid peroxides as predictive of symptomatic vasospasm and poor outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.2002.97.6.1302 ◽

2002 ◽

Vol 97 (6) ◽

pp. 1302-1305 ◽

Cited By ~ 34

Author(s):

Takao Kamezaki ◽

Kiyoyuki Yanaka ◽

Sohji Nagase ◽

Keishi Fujita ◽

Noriyuki Kato ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Lipid Peroxides ◽

Medical Complication ◽

Content Type ◽

Poor Outcome ◽

Symptomatic Vasospasm ◽

Delayed Cerebral Vasospasm ◽

Fine Print

Object. Cerebral vasospasm remains a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). Reactive oxygen species and subsequent lipid peroxidation are reported to participate in the causes of cerebral vasospasm. This clinical study was performed to investigate the relationships between levels of lipid peroxides in cerebrospinal fluid (CSF) and both delayed cerebral vasospasm and clinical outcome after SAH. Methods. Levels of phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH) in the CSF were measured in 20 patients with aneurysmal SAH. The patients' CSF was collected within 48 hours of hemorrhage onset and on Day 6 or 7 post-SAH. On Day 7, angiography was performed to verify the degree and extent of the vasospasm. The relationship between the patients' clinical profiles and the levels of lipid peroxides in the CSF were investigated. Both PCOOH and CEOOH were detectable in CSF, and their levels decreased within 7 days after onset of SAH. The levels of CEOOH within 48 hours after onset of hemorrhage were significantly higher in patients in whom symptomatic vasospasm later developed than in patients in whom symptomatic vasospasm did not develop (p = 0.002). Levels of PCOOH measured within 48 hours after onset of hemorrhage were significantly higher in patients with poor outcomes than in patients with good outcomes (p = 0.043). Conclusions. Increased levels of lipid peroxides measured in the CSF during the acute stage of SAH were predictive of both symptomatic vasospasm and poor outcome. Measurements of lipid peroxides in the CSF may be useful prognostically for patient outcomes as well as for predicting symptomatic vasospasm.

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

Surgical Neurology ◽

10.1016/j.surneu.2005.04.014 ◽

2005 ◽

Vol 64 ◽

pp. S2-S5 ◽

Cited By ~ 25

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

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Matrix Metalloproteinases in Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage

Neurology Research International ◽

10.1155/2013/943761 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

Vivek Mehta ◽

Jonathan Russin ◽

Alexandra Spirtos ◽

Shuhan He ◽

Peter Adamczyk ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Matrix Metalloproteinases ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Critical Role ◽

Morbidity And Mortality ◽

Cellular Mechanisms ◽

Delayed Cerebral Vasospasm ◽

Membrane Bound ◽

Existing Data

Delayed cerebral vasospasm is a significant cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). While the cellular mechanisms underlying vasospasm remain unclear, it is believed that inflammation may play a critical role in vasospasm. Matrix metalloproteinasees (MMPs) are a family of extracellular and membrane-bound proteases capable of degrading the blood-rain barrier (BBB). As such, MMP upregulation following SAH may result in a proinflammatory extravascular environment capable of inciting delayed cerebral vasospasm. This paper presents an overview of MMPs and describes existing data pertinent to delayed cerebral vasospasm.

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Cerebrospinal Fluid Tenascin-C in Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Journal of Neurosurgical Anesthesiology ◽

10.1097/ana.0b013e31822aa1f2 ◽

2011 ◽

Vol 23 (4) ◽

pp. 310-317 ◽

Cited By ~ 30

Author(s):

Hidenori Suzuki ◽

Kenji Kanamaru ◽

Masato Shiba ◽

Masashi Fujimoto ◽

Kyoko Imanaka-Yoshida ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Tenascin C

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Concentrations of estradiol, progesterone and testosterone in sefrum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities

BMC Neuroscience ◽

10.1186/s12868-021-00634-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jan Martin ◽

Eva Plank ◽

Bernhard Ulm ◽

Jens Gempt ◽

Maria Wostrack ◽

...

Keyword(s):

Blood Flow ◽

Cerebrospinal Fluid ◽

Cerebral Blood Flow ◽

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Transcranial Doppler ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Cerebral Arteries ◽

Blood Flow Velocities ◽

Flow Velocities

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.

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

Biological Research For Nursing ◽

10.1177/1099800414536261 ◽

2014 ◽

Vol 17 (2) ◽

pp. 185-190 ◽

Cited By ~ 4

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.

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Early permanent cerebrospinal fluid diversion lowers the rate of nosocomial meningitis in aneurysmal subarachnoid hemorrhage

10.21203/rs.2.21401/v1 ◽

2020 ◽

Author(s):

Davide Marco Croci ◽

Martina Dalolio ◽

Soheila Aghlmandi ◽

Ethan Taub ◽

Daniel Zumofen ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Blood Clot ◽

Delayed Cerebral Ischemia ◽

Infectious Complications ◽

Detectable Effect ◽

Catheter Colonization ◽

Delayed Cerebral Vasospasm ◽

Csf Diversion

Abstract Background: Early permanent cerebrospinal fluid (CSF) diversion for hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) might shorten the duration of external ventricular drainage (EVD) and thereby reduce infectious complications. The potential effect on the rate of delayed cerebral vasospasm (DCVS) and associated morbidity has not been studied to date. The objective of this study was to detect any association with EVD-associated infections (EVDAI), symptomatic DCVS, or delayed cerebral ischemia (DCI) by the time of hospital discharge. Methods: A single-center dataset of aSAH patients who received a permanent CSF diversion procedure between 2009 and 2018 was used for the evaluation. The subjects were divided into an “early group” if such a procedure was performed up to 14 days after the ictus, and a “late group” if it was performed from the 15 th day onward. The statistical analysis employed univariable and multivariable logistic regression models. Results: Among 274 consecutive aSAH patients, 39 (14.2 %) had a permanent CSF diversion procedure. While the blood clot burden was similarly distributed, patients with early permanent CSF diversion (20 out of 39, 51.2%) had higher levels of consciousness on admission. Early permanent CSF diversion was associated with a shorter duration of EVD (OR 0.73, 95%CI 0.58-0.92 per day). Higher catheter colonization to EVDAI ratio (1/7 out of 20 vs. 7/7 out of 19) and a markedly lower frequency of EVDAI (OR 0.08, 95 %CI 0.01-0.80) were detected. The prevalence (5 vs. 37) and the cumulative incidence (3 vs. 18) of EVDAI were remarkably lower in patients receiving early permanent CSF diversion. The occurrence of CSF-diversion device obstruction, the rate of symptomatic DCVS (OR 0.61, 95 %CI 0.16-2.27) or detected DCI on computed tomography (OR 0.35, 95 %CI 0.08-1.47), and the likelihood of a poor outcome at discharge did not differ between the two groups (OR 0.88, 95%CI 0.24-3.22). Conclusions: Early permanent CSF diversion in good grade aSAH patients is associated with a shorter duration of EVD, lower catheter colonization rates, and fewer infectious complications. The timing of permanent CSF diversion had no detectable effect on DCVS-related morbidity. These findings need to be confirmed in larger cohorts.

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