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Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction.

ABSTRACT: INTRODUCTION:We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction (MMI) and elucidate their underlying regulatory mechanisms. METHODS:We first developed a cytokine profile by Quantibody® Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non-acute cerebral infarction (NACI). The differentially expressed cytokines were then identified in patients with MMI using two-tailed Student's t-test and Fisher's Exact Test compared with patients with NACI. Gene Ontology and pathway enrichment analyses were performed using DAVID. Protein-protein interaction (PPI) network was constructed based on STRING database. RESULTS:A total of 10 differentially expressed cytokines were identified from 320 unique inflammatory cytokines in serums. Among them, four cytokines, like NCAM1 (neural cell adhesion molecule 1), IGFBP-6 (insulin-like growth factor binding protein 6), LYVE1 (lymphatic vessel endothelial hyaluronan receptor 1), and LCN2 (Lipocalin2), were up-regulated, while another six cytokines, such as TGFB1 (transforming growth factor, beta 1, also known as LAP), EGF (epidermal growth factor), PDGFA (platelet-derived growth factor alpha polypeptide), MMP-10 (matrix metallopeptidase 10), IL-27 (interleukin 27), and CCL2 (chemokine (C-C motif) receptor 2), were down-regulated. Moreover, cytokine-cytokine receptor interaction pathway was significantly enriched. CONCLUSIONS:Our findings indicate that 10 differentially expressed cytokines, such as NCAM1, LCN2, IGFBP-6, LYVE1, MMP-10, IL-27, PDGFA, EGF, CCL2, and TGFB1 may participate in the development of MMI. Moreover, cytokine-cytokine receptor interaction pathway may be an important mechanism involved in this disease. These differentially expressed cytokines may serve as diagnostic biomarkers or drug targets for MMI.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC5561308 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction.

Zhou Zhonghe Z Zhang Jinghua J Li Xiaoqiu X Xia Cheng C Han Yaling Y Han Yaling Y Chen Huisheng H

Brain and behavior 20170707 8

<h4>Introduction</h4>We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction (MMI) and elucidate their underlying regulatory mechanisms.<h4>Methods</h4>We first developed a cytokine profile by Quantibody<sup>®</sup> Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non-acute cerebral infarction (NACI). The differentially expressed cytokines were then identified in patients with MMI using two-tail ...[more]

PMID: 28828208

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Project description:BackgroundMalignant middle cerebral artery infarction is a potentially life-threatening disease. Decompressive hemicraniectomy constitutes an evidence-based treatment practice, especially in patients under 60 years of age; however, recommendations with respect to postoperative management and particularly duration of postoperative sedation lack standardization.ObjectiveThis survey study aimed to analyze the current situation of patients with malignant middle cerebral artery infarction following hemicraniectomy in the neurointensive care setting.Material and methodsFrom 20 September 2021 to 31 October 2021, 43 members of the initiative of German neurointensive trial engagement (IGNITE) network were invited to participate in a standardized anonymous online survey. Descriptive data analysis was performed.ResultsOut of 43 centers 29 (67.4%) participated in the survey, including 24 university hospitals. Of the hospitals 21 have their own neurological intensive care unit. While 23.1% favored a standardized approach regarding postoperative sedation, the majority utilized individual criteria (e.g., intracranial pressure increase, weaning parameters, complications) to assess the need and duration. The timing of targeted extubation varied widely between hospitals (≤ 24 h 19.2%, ≤ 3 days in 30.8%, ≤ 5 days in 19.2%, > 5 days in 15.4%). Early tracheotomy (≤ 7 days) is performed in 19.2% and 80.8% of the centers aim for tracheotomy within 14 days. Hyperosmolar treatment is used on a regular basis in 53.9% and 22 centers (84.6%) agreed to participate in a clinical trial addressing the duration of postoperative sedation and ventilation.ConclusionThe results of this nationwide survey among neurointensive care units in Germany reflect a remarkable heterogeneity in the treatment practices of patients with malignant middle cerebral artery infarction undergoing hemicraniectomy, especially with respect to the duration of postoperative sedation and ventilation. A randomized trial in this matter seems warranted.

Project description:A disrupted blood-brain barrier (BBB) with extravasation of macromolecules plays a critical role in the development of malignant middle cerebral artery infarction (MMI). Proteinuria is considered a marker of generalized endothelial dysfunction, including BBB disruption. This study aimed to clarify whether proteinuria identified in the acute stage of stroke is associated with MMI development. Patients with infarctions involving the middle cerebral artery territory were reviewed. Urine samples collected within 8 hours after stroke were analyzed using urine dipsticks. Patients were divided into proteinuria (urine dipstick reading of 1 + to 4+) and nonproteinuria groups. MMI was present if either signs of uncal herniation or a progressive conscious disturbance were recorded along with a midline shift > 5 mm identified on follow-up computed tomography (CT). Among the 1261 patients identified between January 2010 and June 2019, 138 were eligible for final analyses. Patients in the MMI group had lower Alberta Stroke Program Early CT Scores (ASPECTS), higher National Institutes of Health Stroke Scale scores, and a greater proportion of proteinuria than those in the non-MMI group. Four multivariate logistic regression models were used to clarify the role of proteinuria in MMI development. In model 1, proteinuria was significantly associated with MMI after adjusting for age, sex, dyslipidemia and ASPECTS (OR = 2.987, 95% CI = 1.329-6.716, P = .0081). The risk of developing MMI in patients with proteinuria remained significant in model 2 (OR = 3.066, 95% CI = 1.349-6.968, P = .0075) after adjusting for estimated glomerular filtrate rate (eGFR) < 60ml/min/1.73 m2 in addition to variables in model 1. In model 3, proteinuria was still significantly associated with MMI after adjusting for age, sex, dyslipidemia, ASPECTS, hypertension, diabetes, and atrial fibrillation (OR = 2.521, 95% CI = 1.075-5.912, P = .0335). In model 4, the risk of developing MMI in patients with proteinuria remained significant (OR = 2.579, 95% CI = 1.094-6.079, P = .0304) after adjusting for eGFR < 60ml/min/1.73 m2 in addition to variables in model 3. Proteinuria is independently associated with MMI development. Proteinuria may be a clinically accessible predictor of MMI development.

Project description:AbstractDisrupted blood-brain barrier (BBB) in patients with ischemic stroke plays a critical role in malignant middle cerebral artery infarction (MMI) development.Cerebral white matter changes (WMC), particularly in the deep subcortical area or in severe one, may be also underlain by disrupted BBB. It is unclear whether the presence of WMC with potential premorbid disruption of BBB makes patients susceptible to MMI. Therefore, this study aimed to clarify any putative relationship between the MMI and WMC in terms of their severity and locations.In this case-control study, patients with infarction in the middle cerebral artery territory were retrospectively reviewed. Brain magnetic resonance images were analyzed according to Fazekas scale, and identified WMC were divided into periventricular WMC (PV-WMC) and deep subcortical WMC (deep-WMC). Patients were scored as having WMC, PV-WMC, deep-WMC, severe PV-WMC, and severe deep-WMC according to the severity and locations. Patients were defined as having MMI if either a progressive conscious disturbance or signs of uncal herniation was recorded in combination with a midline shift >5 mm identified on the follow-up computed tomography.Among 297 patients admitted between July 2009 and February 2015, 92 patients were eligible for final analysis. Compared to patients without MMI, patients with MMI had a higher score of National Institutes of Health Stroke Scale, a larger infarct volume, and an increasingly greater proportion of severe PV-WMC, deep-WMC, and severe deep-WMC, respectively. After adjustment for sex, age, infarct volume, and history of hypertension, severe deep-WMC (odds ratio [OR] = 6.362, 95% confidence interval [CI] = 1.444-28.023, P = .0144) and severe PV-WMC (odds ratio = 5.608, 95% confidence interval = 1.107-28.399, P = .0372) were significantly associated with MMI development.MMI and WMC are significantly associated such that MMI development is more likely when PV-WMC or deep-WMC is more severe. We hypothesize that Fazekas scale-defined severe deep-WMC and PV-WMC may be considered as clinically approachable predictors of MMI development. These findings support that the WMC with potential premorbid disrupted BBB may make patients susceptible to MMI, and further prospective study should be conducted to clarify this hypothesis.

Project description:Introduction Decompressive hemicraniectomy (DCE) is routinely performed for intracranial pressure control after malignant middle cerebral artery (MCA) infarction. Decompressed patients are at risk of traumatic brain injury and the syndrome of the trephined until cranioplasty. Cranioplasty after DCE is itself associated with high complication rates. Single-stage surgical strategies may eliminate the need for follow-up surgery while allowing for safe brain expansion and protection from environmental factors. Research question Assess the volume needed for safe expansion of the brain to enable single-stage surgery. Materials and methods We performed a retrospective radiological and volumetric analysis of all patients that had DCE in our clinic between January 2009 and December 2018 and met inclusion criteria. We investigated prognostic parameters in perioperative imaging and assessed clinical outcome. Results Of 86 patients with DCE, 44 fulfilled the inclusion criteria. Median brain swelling was 75.35 mL (8.7–151.2 mL). Median bone flap volume was 113.3 mL (73.34–146.1 mL). Median brain swelling was 1.62 mm below the previous outer rim of the skull (5.3 mm to –2.19 mm). In 79.6% of the patients, the volume of removed bone alone was equivalent to or larger than the additional intracranial volume needed for brain swelling. Discussion and conclusion The space provided by removal of the bone alone was sufficient to match the expansion of the injured brain after malignant MCA infarction in the vast majority of our patients A subgaleal space-expanding flap with a minimal offset can provide protection from trauma and atmospheric pressure without compromising brain expansion. Highlights • Volume augmentation of the swollen brain is smaller than the volume of removed bone in 79.6% of cases.• An additional Volume of about 50 mL would have provided adequate space for the swollen brain in all cases.• Maximum modeled brain swelling outside of the previous skull limit is 2.19 mm.

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Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction.

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Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction.

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