RNase A Inhibits Formation of Neutrophil Extracellular Traps in Subarachnoid Hemorrhage

Früh, A.; Tielking, Katharina; Schoknecht, Felix; Liu, Shuheng; Schneider, Ulf C.; Fischer, Silvia; Vajkoczy, Peter; Xu, Rihao

doi:10.3389/fphys.2021.724611

Cited by 16 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A prior study aimed to detect NET markers in mice and in patients with SAH ( 23 ). This study used ds-DNA as a surrogate for the presence of NETs.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, NETs can be therapeutically targeted by degradation with DNAses, as demonstrated in animal studies (17)(18)(19) and ex vivo thrombolysis experiments (14,20). While an inflammatory surge and an increased neutrophillymphocyte ratio have been linked to vasospasm progression, DCI, and outcome after aSAH, only limited data is available on the detection of NETs in patients with SAH (21)(22)(23)(24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Witsch

Spalart

Martinod

et al. 2022

Critical Care Explorations

View full text Add to dashboard Cite

IMPORTANCE: Myeloperoxidase (MPO)-DNA complexes, biomarkers of neutrophil extracellular traps (NETs), have been associated with arterial and venous thrombosis. Their role in aneurysmal subarachnoid hemorrhage (aSAH) is unknown. OBJECTIVES: To assess whether serum MPO-DNA complexes are present in patients with aSAH and whether they are associated with delayed cerebral ischemia (DCI). DESIGN, SETTING, AND PARTICIPANTS: Post-hoc analysis of a prospective, observational single-center study, with de novo serum biomarker measurements in consecutive patients with aSAH between July 2018 and September 2020, admitted to a tertiary care neuroscience ICU. MAIN OUTCOMES AND MEASURES: We analyzed serum obtained at admission and hospital day 4 for concentrations of MPO-DNA complexes. The primary outcome was DCI, defined as new infarction on brain CT. The secondary outcome was clinical vasospasm, a composite of clinical and transcranial Doppler parameters. We used Wilcoxon signed-rank-test to assess for differences between paired measures. RESULTS: Among 100 patients with spontaneous subarachnoid hemorrhage, mean age 59 years (sd ± 13 yr), 55% women, 78 had confirmed aSAH. Among these, 29 (37%) developed DCI. MPO-DNA complexes were detected in all samples. The median MPO-DNA level was 33 ng/mL (interquartile range [IQR], 18–43 ng/mL) at admission, and 22 ng/mL (IQR, 11–31 ng/mL) on day 4 (unpaired test; p = 0.015). We found a significant reduction in MPO-DNA levels from admission to day 4 in patients with DCI (paired test; p = 0.036) but not in those without DCI (p = 0.17). There was a similar reduction in MPO-DNA levels between admission and day 4 in patients with (p = 0.006) but not in those without clinical vasospasm (p = 0.47). CONCLUSIONS AND RELEVANCE: This is the first study to detect the NET biomarkers MPO-DNA complexes in peripheral serum of patients with aSAH and to associate them with DCI. A pronounced reduction in MPO-DNA levels might serve as an early marker of DCI. This diagnostic potential of MPO-DNA complexes and their role as potential therapeutic targets in aSAH should be explored further.

show abstract

“…A prior study aimed to detect NET markers in mice and in patients with SAH ( 23 ). This study used ds-DNA as a surrogate for the presence of NETs.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Witsch

Spalart

Martinod

et al. 2022

Critical Care Explorations

View full text Add to dashboard Cite

show abstract

“…A prior study aimed to detect NET markers in mice and in patients with SAH. 22 This study used double stranded DNA (ds-DNA) as a surrogate for the presence of NETs. However, ds-DNA has been shown to be an unspecific remnant of cell death 26 .…”

Section: Discussionmentioning

confidence: 99%

“…13,19 While excess inflammation and increased neutrophil lymphocyte ratios have been linked to DCI and outcome after aSAH, only limited data is available on the detection of NETs in patients with SAH. [20][21][22] In this exploratory study we focused on one major NET biomarker, myeloperoxidase (MPO)-DNA complexes. We leveraged prospective data from a cohort of patients with SAH undergoing prospective neurological and transcranial Doppler (TCD) exams, as well as standardized DCI assessment.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil Extracellular Trap Biomarker Titers and Delayed Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage

Witsch

Spalart

Martinod

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Myeloperoxidase (MPO)-DNA complexes have been associated with arterial and venous thrombosis. Their role in patients with aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Here, we sought to explore whether serum MPO-DNA-complexes are present in patients with aSAH, and whether levels of serum MPO-DNA complexes are associated with delayed cerebral ischemia (DCI). Methods: We performed a post-hoc analysis of a prospective, blinded, observational single-center biomarker study that enrolled consecutive patients with spontaneous SAH between July 2018 and September 2020. Serum samples obtained on admission and on hospital day 4 were analyzed for concentrations of MPO-DNA complexes. The primary outcome was the occurrence of DCI defined as new infarction on brain CT-scan. The secondary outcome was clinical vasospasm, a composite of clinical and transcranial doppler parameters. We used Wilcoxon's signed-rank-test to assess for differences between paired measures. Results: Among 100 patients with spontaneous SAH, mean age 59 (SD+13) years, 55% women, 78 patients had an aneurysmal SAH and complete DCI information. Among these, 29 (37%) developed DCI. MPO-DNA complexes were detected in all serum samples. The median MPO-DNA level was 33 ng/ml (IQR, 18-43 ng/ml) on admission, and 22 ng/ml (IQR, 11-31 ng/ml) on day 4 (Mann-Whitney test: p=0.015). In the primary outcome analysis, we found a significant reduction in MPO-DNA levels from admission to day 4 in patients with DCI (paired test, p=0.036) but not in those without DCI (p=0.171). The secondary analysis showed a similar reduction in MPO-DNA levels between admission and day 4 in patients with (p=0.006), but not in those without clinical vasospasm (p=0.473). Conclusions: MPO-DNA-complexes are detectable in peripheral serum samples of patients with aSAH. A pronounced reduction in MPO-DNA levels over the first days after aSAH might herald DCI. The potential of MPO-DNA serum levels to serve as a biomarker of DCI requires further exploration.

show abstract

Analysis of Cerebral Spinal Fluid Drainage and Intracranial Pressure Peaks in Patients with Subarachnoid Hemorrhage

Früh,

Truckenmüller,

Wasilewski

et al. 2024

Neurocrit Care

View full text Add to dashboard Cite

Background After aneurysmal subarachnoid hemorrhage (aSAH), elevated intracranial pressure (ICP) due to disrupted cerebrospinal fluid (CSF) dynamics is a critical concern. An external ventricular drainage (EVD) is commonly employed for management; however, optimal strategies remain debated. The randomized controlled Earlydrain trial showed that an additional prophylactic lumbar drainage (LD) after aneurysm treatment improves neurological outcome. We performed a post hoc investigation on the impact of drainage volumes and critical ICP values on patient outcomes after aSAH. Methods Using raw patient data from Earlydrain, we analyzed CSF drainage amounts and ICP measurements in the first 8 days after aSAH. Outcomes were the occurrence of secondary infarctions and the score on the modified Rankin scale after 6 months, dichotomized in values of 0–2 as favorable and 3–6 as unfavorable. Repeated measurements were considered with generalized estimation equations. Results Earlydrain recruited 287 patients, of whom 221 received an EVD and 140 received an LD. Higher EVD volumes showed a trend to more secondary infarctions (p = 0.09), whereas higher LD volumes were associated with less secondary infarctions (p = 0.009). The mean total CSF drainage was 1052 ± 659 mL and did not differ concerning infarction and neurological outcome. Maximum ICP values were higher in patients with poor outcomes but not related to drainage volumes via EVD. After adjustment for aSAH severity and total CSF drainage, higher LD volume was linked to favorable outcome (per 100 mL: odds ratio 0.61 (95% confidence interval 0.39–0.95), p = 0.03), whereas higher EVD amounts were associated with unfavorable outcome (per 100 mL: odds ratio 1.63 (95% confidence interval 1.05–2.54), p = 0.03). Conclusions Findings indicate that effects of CSF drainage via EVD and LD differ. Higher amounts and higher proportions of LD volumes were associated with better outcomes, suggesting a potential quantity-dependent protective effect. Optimizing LD volume and mitigating ICP spikes may be a strategy to improve patient outcomes after aSAH. Clinical trial registration: ClinicalTrials.gov identifier: NCT01258257.

show abstract

RNase A Inhibits Formation of Neutrophil Extracellular Traps in Subarachnoid Hemorrhage

Cited by 16 publications

References 45 publications

Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Neutrophil Extracellular Trap Biomarker Titers and Delayed Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage

Analysis of Cerebral Spinal Fluid Drainage and Intracranial Pressure Peaks in Patients with Subarachnoid Hemorrhage

Contact Info

Product

Resources

About