Dataset Information

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

ABSTRACT:

Background

Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology.

Objective

To explore the vitamin D system as a potential treatment for CVS.

Methods

25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during the months with a peak vs nadir of VitD3 values were analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm/outcome data in SAH patients admitted in 2017. An experimental mice SAH model and cell culture model were used to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25-VitD3). Additionally, the mediators acting in the VitD mechanism were researched and detected.

Results

Based on the retrospective analysis demonstrating an increased frequency of vasospasm in SAH patients during the low vitamin D period in winter, we started basic research experiments. Active 1,25-VitD3 hormone attenuated CVS, neurological deficit, and inflammation after intrathecal blood injection in mice. Deletion of the vitamin D receptor in the endothelium or in myeloid cells decreased the protective 1,25-VitD3 effect. Co-culture experiments of myeloid and endothelial cells with blood confirmed the anti-inflammatory 1,25-VitD3 effect but also revealed an induction of stroma-cell-derived factor 1? (SDF1?), vascular endothelial growth factor, and endothelial nitric oxide synthase by 1,25-VitD3. In mice, SDF1? mimicked the protective effect of 1,25-VitD3 against CVS. From bench to bedside, CVS severity was inversely correlated with vitamin D plasma level, prospectively. Patients with more severe CVS exhibited attenuated expression of SDF1? and 1,25-VitD3-responsive genes on circulating myeloid cells.

Conclusion

1,25-VitD3 attenuates CVS after SAH by inducing SDF1?. However, VitD administration should be tested as optional treatment to prevent CVS.

SUBMITTER: Kashefiolasl S

PROVIDER: S-EPMC7884149 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

Kashefiolasl Sepide S Leisegang Matthias S MS Helfinger Valeska V Schürmann Christoph C Pflüger-Müller Beatrice B Randriamboavonjy Voahanginirina V Vasconez Andrea E AE Carmeliet Geert G Badenhoop Klaus K Hintereder Gudrun G Seifert Volker V Schröder Katrin K Konczalla Juergen J Brandes Ralf P RP

Neurosurgery 20210201 3

<h4>Background</h4>Cerebral vasospasm (CVS) is a frequent complication after subarachnoid hemorrhage (SAH), with no sufficient therapy and a complex pathophysiology.<h4>Objective</h4>To explore the vitamin D system as a potential treatment for CVS.<h4>Methods</h4>25-vitamin D3 levels tested between 2007 and 2015 and data of SAH patients admitted during the months with a peak vs nadir of VitD3 values were analyzed, retrospectively. We prospectively correlated VitD3 and vasospasm/outcome data in S ...[more]

PMID: 33269399

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Project description:The diagnosis of cerebral vasospasm after Subarachnoid-Hemorrhage is currently very difficult, additional tools such as blood biomarkers are necessary. We tested the ability of gene expression profiles of blood cells to predict vasospasm. 32 patients suffering subarachnoid-hemorrhage were included in this prospective monocentre study. They were grouped according to have a complicated cerebral vasospasm (Vasospasm) or not (Control) and Paired according to age (+/- 10 years), sex, Fisher grade (+/- 1), location, smoking (at least 3 first parameters). Gene expression profiles of blood cells were determined using 25,000~gene microarray. Blood sample: 2.5 mL harvested in PAXgene® Blood RNA tubes (PreAnalytix) RNA extraction: PAXgene® Blood RNA kit (Qiagen). We used a Universel Reference RNA (Stratagene). RNA amplification and labelling: kit Amino Allyl MessageAmp II (Ambion). We hybridized 4 microarrays per patient using pangenomic microarrays from the "Réseau National des Génopôles" (Illkirch, France). 2 slides were hybridized with reference RNA labelled Cy3 and patient RNA labelled Cy5, and 2 slides were hybridized with reference RNA labelled Cy5 and patient RNA labelled Cy3. Hybridation : Agilent protocol with few modifications : 750 ng of each labelled RNA were hubriddized at 60°C during 17 hours in an Aglient hybridization oven. After washings, Slides were scanned with a GenePix 4000B scanner (Molecular Devices). Image intensity data were extracted with GenePix Pro 6.0 analysis software. Quantification of Cy3 and Cy5 and selection of good spots were performed using the MAIA software (Novikov E and Barillot E. Software package for automatic microarray image analysis (MAIA). The ACUITY software was then used to normalize log ratios Cy3/Cy5 with Lowess non linear normalization, to filter out genes not present in at least 3 slides out of 4, to evaluate the reproducibility of the 4 microarrays of each patient (hierarchical clustering, Self Organizing Maps). Statistical analyses to insure reproducibility was performed using Excel (correlation coefficients, ANOVA). Only slides that passed all reprocubility tests were validated.

Project description:IntroductionCerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH.MethodsWe retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction.Results343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3-4) and poor Hunt-Hess grade (4-5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ?53 years, leukocyte count ?11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ?11× 109/L on admission and aneurysm size ? 10 mm were independent risk factors of SV. Serum glucose level ?7.0 mmol/L on admission was an independent risk factor of AV.ConclusionRisk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend early and aggressive therapy in these patients at-risk of CVS.

Dataset Information

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

Background

Objective

Methods

Results

Conclusion

Publications

Vitamin D-A New Perspective in Treatment of Cerebral Vasospasm.

Similar Datasets

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