Clusterin, a New Cerebrospinal Fluid Biomarker in Severe Subarachnoid Hemorrhage: A Pilot Study

2017 ◽  
Vol 107 ◽  
pp. 424-428 ◽  
Author(s):  
Norbert Wąsik ◽  
Bartosz Sokół ◽  
Marcin Hołysz ◽  
Witold Mańko ◽  
Robert Juszkat ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Pilot Study ◽  
Fluid Biomarker

scholarly journals Toll-like receptor linked cytokine profiles in cerebrospinal fluid discriminate neurological infection from sterile inflammation

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Simone M Cuff ◽  
Joseph P Merola ◽  
Jason P Twohig ◽  
Matthias Eberl ◽  
William P Gray
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Practice ◽  
Inflammatory Response ◽  
Nosocomial Infection ◽  
Pathway Analysis ◽  
Interleukin 6 ◽  
Sterile Inflammation ◽  
Interleukin 17 ◽  
Toll Like Receptor ◽  
Fluid Biomarker

Abstract Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

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.

O2-07-03: Validating predicted biological effects of Alzheimer's disease associated SNPs using cerebrospinal fluid biomarker levels

2010 ◽  
Vol 6 ◽  
pp. S112-S113 ◽  
Author(s):  
John S.K. Kauwe ◽  
Carlos Cruchaga ◽  
Sarah Bertelsen ◽  
Kevin Mayo ◽  
Wayne Latu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Biological Effects ◽  
Fluid Biomarker

Abstract TMP23: Inflammasome-derived Caspase-1 is Elevated in the Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients and Correlated to Outcome

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yonatan Hirsch ◽  
Joseph R Geraghty ◽  
Eitan A Katz ◽  
Jeffrey A Loeb ◽  
Fernando Testai
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
External Ventricular Drain ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Normal Brain ◽  
Poor Outcome ◽  
Caspase 1 ◽  
Initial Severity ◽  
Poor Outcomes

Introduction: The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome. Methods: SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA). Results: Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004). Conclusions: The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.

Abstract T P351: Unbound Iron and Ceruloplasmin Levels in Cerebrospinal Fluid Are Associated with Development of Deep Cerebral Infarcts Following Subarachnoid Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Lauren Koffman ◽  
Gabor Toth ◽  
M. Shazam Hussain ◽  
Magdy Selim ◽  
Peter Rasmussen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarcts ◽  
Active Iron ◽  
Redox Active ◽  
Wilcoxon Rank Sum Test ◽  
Radiological Data ◽  
Experimental Subarachnoid Hemorrhage ◽  
Preliminary Study ◽  
Iron Redox

Introduction: Iron-dependent formation of reactive oxygen species has been implicated in the development of vasospasm (VSP) and neuronal injury following experimental subarachnoid hemorrhage (SAH). We report the association between unbound (“free”) iron in CSF of SAH patients and the risk of angiographic vasospasm and cerebral infarcts (CI) on neuroimaging from a recently completed pilot study. Methods: Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure redox active iron (REDOX-Fe). Ceruloplasmin (Cp) concentration and levels of malondialdehyde (MDA), a marker of lipid peroxidation were also measured. We prospectively collected and recorded demographic, clinical, and radiological data. Logistic regression and Wilcoxon Rank Sum test were used. Results: Five of 12 patients developed angiographic VSP (41.6%) and eight developed CI (66.6%). Mean REDOX-Fe was higher in patients with CI (3.96 ± 0.97 Vs. 2.77 ± 0.87 mcg/dl, p 0.07), particularly in patients with deep-seated strokes (4.56 ± 0.67 Vs. 3.35 ± 0.89, p 0.03). Levels of Cp at day 3 were lower in patients with deep strokes (34,092 ± 23,780 Vs. 86,045 ± 34,752 ng/ml, p 0.03). A trend towards higher REDOX-Fe on day 3 in patients who developed VSP (4.52 ± 1.16 Vs. 2.96 ± 0.71, p 0.07), and lower Cp levels on day 5 (45,033 ± 29,079 Vs. 63,044 ± 24,821, p 0.1) was found. Levels of MDA were higher in patients who developed CI (10.36 ± 4.36 Vs. 5.9 ± 4.2 nmol, p 0.08). Conclusions: In this preliminary study we found higher concentrations of redox active iron in CSF of SAH patients who develop deep-seated CI on neuroimaging. Evidence of increased oxidative damage correlated with development of CI. A possible association between non-protein bound iron and angiographic VSP is suggested as well. Ceruloplasmin may exert a protective effect in this setting. Further studies are needed to validate these findings.

Sign in / Sign up

Export Citation Format

Share Document