scholarly journals Human cerebrospinal fluid microRNA: temporal changes following subarachnoid hemorrhage

2016 ◽  
Vol 48 (5) ◽  
pp. 361-366 ◽  
Author(s):  
Ciarán J. Powers ◽  
Ryan Dickerson ◽  
Stacey W. Zhang ◽  
Cameron Rink ◽  
Sashwati Roy ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Messenger Rna ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Temporal Changes ◽  
Rna Molecules ◽  
Human Cerebrospinal Fluid ◽  
Over Time

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of hemorrhagic stroke with 30-day mortality between 33 and 45%. Delayed cerebral ischemia (DCI) is the chief cause of morbidity and mortality in patients who survive the initial aSAH. DCI accounts for almost 50% of deaths in patients surviving to treatment of the ruptured aneurysm. The mechanisms for brain injury after aSAH and the brain's response to this injury are not fully understood in humans. MicroRNAs (miRs) are 22- to 25-nucleotide single-stranded RNA molecules that inhibit the expression of specific messenger RNA targets. In this work, miR profiling of human cerebrospinal fluid from eight patients after aSAH was performed daily for 10 days with the goal of identifying changes in miR abundance. Using the nanoString nCounter Expression Assay, we identified two specific clusters of miR that were differentially regulated over time. Quantitative RT-PCR was performed on select miRs from each cluster. The first cluster contained miRs known to be present in blood and decreased in abundance over time. miRs in this group include miR-92a and let-7b. The second cluster contained several poorly characterized miRs that increased in abundance over time. miRs in this group included miR-491. This second cluster of miRs may be released into the CSF by the brain itself as a result of the initial SAH. Temporal changes in the abundance of specific miRs in human CSF after aSAH may provide novel insight into the role of miRs in brain injury and the brain's response.

scholarly journals Cerebrospinal Fluid 20-HETE Is Associated With Delayed Cerebral Ischemia and Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽  
2011 ◽  
Vol 42 (7) ◽  
pp. 1872-1877 ◽  
Author(s):  
Elizabeth A. Crago ◽  
Bhavani P. Thampatty ◽  
Paula R. Sherwood ◽  
Chie-Wen J. Kuo ◽  
Catherine Bender ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Poor Outcomes

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 Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sami Ridwan ◽  
Alexander Grote ◽  
Matthias Simon
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Interleukin 6 ◽  
Time Course ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Interindividual Variations ◽  
Potential Biomarker ◽  
Diagnostic Usefulness

AbstractInterleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

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

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.

Emerging Markers of Early Brain Injury and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

2017 ◽  
Vol 107 ◽  
pp. 148-159 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
Krishna Amuluru ◽  
Brendan Smith ◽  
Nitesh Damodara ◽  
Mohammad El-Ghanem ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury

scholarly journals Role of Damage Associated Molecular Pattern Molecules (DAMPs) in Aneurysmal Subarachnoid Hemorrhage (aSAH)

2018 ◽  
Vol 19 (7) ◽  
pp. 2035 ◽  
Author(s):  
Shafqat Chaudhry ◽  
Ahmad Hafez ◽  
Behnam Rezai Jahromi ◽  
Thomas Kinfe ◽  
Alf Lamprecht ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Therapy Monitoring ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Endovascular Coiling ◽  
Molecular Pattern ◽  
Extracellular Matrix Components

Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mechanisms leading to these complications are complex and poorly understood. Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response. Hence, the events during early brain injury can influence the occurrence of delayed brain injury. Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives. DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury. Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1α, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.

scholarly journals Measuring the Impact of Delayed Cerebral Ischemia on Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage—Protocol of a Swiss Nationwide Observational Study (MoCA–DCI Study)

Neurosurgery ◽  
2018 ◽  
Vol 84 (5) ◽  
pp. 1124-1132 ◽  
Author(s):  
Martin N Stienen ◽  
Christian Fung ◽  
Philippe Bijlenga ◽  
Daniel W Zumofen ◽  
Rodolfo Maduri ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Observational Study ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Patient Specific ◽  
Neuropsychological Outcome ◽  
The Relationship ◽  
Baseline Examination

AbstractBACKGROUNDThe exact relationship between delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and neuropsychological impairment remains unknown, as previous studies lacked a baseline examination after aneurysm occlusion but before the DCI-period. Neuropsychological evaluation of acutely ill patients is often applied in a busy intensive care unit (ICU), where distraction represents a bias to the obtained results.OBJECTIVETo evaluate the relationship between DCI and neuropsychological outcome after aSAH by comparing the Montreal Cognitive Assessment (MoCA) results in aSAH patients with and without DCI at 3 mo with a baseline examination before the DCI-period (part 1). To determine the reliability of the MoCA, when applied in an ICU setting (part 2).METHODSProspective, multicenter, and observational study performed at all Swiss neurovascular centers. For part 1, n = 240 consecutive aSAH patients and for part 2, n = 50 patients with acute brain injury are recruited.EXPECTED OUTCOMESPart 1: Effect size of the relationship between DCI and neuropsychological outcome (MoCA). Part 2: Reliability measures for the MoCA.DISCUSSIONThe institutional review boards approved this study on July 4, 2017 under case number BASEC 2017-00103. After completion, the results will be offered to an international scientific journal for peer-reviewed publication. This study determines the exact impact of DCI on the neuropsychological outcome after aSAH, unbiased by confounding factors such as early brain injury or patient-specific characteristics. The study provides unique insights in the neuropsychological state of patients in the early period after aSAH.

scholarly journals Lipocalin-Type Prostaglandin D Synthase Scavenges Biliverdin in the Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Hemorrhage

2014 ◽  
Vol 34 (9) ◽  
pp. 1558-1567 ◽  
Author(s):  
Takashi Inui ◽  
Mitsuhito Mase ◽  
Ryoko Shirota ◽  
Mariko Nagashima ◽  
Tetsuya Okada ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Major Protein ◽  
Endogenous Ligand ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Human Cerebrospinal Fluid ◽  
Prostaglandin D Synthase ◽  
A Minor

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is the second major protein in human cerebrospinal fluid (CSF) and belongs to the lipocalin superfamily composed of various secretory lipophilic ligand transporter proteins. However, the endogenous ligand of L-PGDS has not yet been elucidated. In this study, we purified L-PGDS from the CSF of aneurysmal subarachnoid hemorrhage (SAH) patients. Lipocalin-type PG D synthase showed absorbance spectra with major peaks at 280 and 392 nm and a minor peak at around 660 nm. The absorbance at 392 nm of L-PGDS increased from 1 to 9 days and almost disappeared at 2 months after SAH, whereas the L-PGDS activity decreased from 1 to 7 days and recovered to normal at 2 months after SAH. These results indicate that some chromophore had accumulated in the CSF after SAH and bound to L-PGDS, thus inactivating it. Matrix assisted laser desorption ionization time-of-flight mass spectrometry of L-PGDS after digestion of it with endoproteinase Lys-C revealed that L-PGDS had covalently bound biliverdin, a by-product of heme breakdown. These results suggest that L-PGDS acted as a scavenger of biliverdin, which is a molecule not found in normal CSF. This is the first report of identification of a pathophysiologically important endogenous ligand for this lipocalin superfamily protein in humans.

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