Dataset Information

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study.

ABSTRACT:

Background

Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue.

Methods

In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal.

Results

We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments.

Conclusion

This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

SUBMITTER: Tobieson L

PROVIDER: S-EPMC7382826 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study.

Tobieson Lovisa L Czifra Zita Z Wåhlén Karin K Marklund Niklas N Ghafouri Bijar B

Proteome science 20200725

<h4>Background</h4>Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro<i>,</i> however, protein adsorption to CMD membranes has not been characterized following implantation in human b ...[more]

PMID: 32728348

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Project description:PurposeSpontaneous intracerebral hemorrhage (ICH) cases caused by hypertension often have poor prognoses. The use of dehydrant agents, such as mannitol, is common to reduce intracranial pressure and alleviate cerebral edema, but they may also pose a risk of worsening kidney function. This study aimed to investigate the impact of impaired kidney function on the outcomes of surgically treated hypertensive ICH patients.MethodsWe conducted a retrospective analysis of a consecutive cohort of patients who underwent surgical intervention due to hypertension-related ICH at our institute between December 1, 2017, and January 31, 2022. Demographic, clinical, radiological, and prognostic data were collected. Patients were categorized into two groups based on 90-day mortality: group A [overall survival (OS) ≤3 months] and group B (OS >3 months). Survival analysis was performed to identify factors associated with poor outcomes.ResultsAmong the 232 eligible patients, group A exhibited significantly impaired kidney function, as indicated by mean estimated glomerular filtration rate (eGFR) at admission, postoperative, 3-day postoperative, and 7-day postoperative time points (91.9, 82.5, 73.5, 75.2 ml/min/1.73 m²). In contrast, group B did not show significant changes in kidney function (mean eGFR for the corresponding time points: 108.1, 106.5, 111.5, 109.6 ml/min/1.73 m²). The 3-day postoperative eGFR showed the strongest predictive ability for assessing prognosis [areas under the curve (AUC): 0.617, 0.675, 0.737, 0.730]. Univariate and multivariate analyses identified low Glasgow Coma Scale (GCS) score (3-8), ventricle intrusion of hematomas, cardiac failure, larger hematoma volume, infection, and lower 3-day postoperative eGFR as adverse factors for survival.ConclusionsPreserving kidney function is crucial for achieving favorable outcomes in hypertensive ICH cases. Impaired 3-day postoperative eGFR emerged as an independent risk factor for overall survival. Patients with cardiac failure, infection, and larger hematoma volume should receive careful management to improve outcomes.

Project description:Background and purposeIntracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment.MethodsWe analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment.ResultsWe followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14-2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12-2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51-0.94]), and to benefit from antidepressant therapy (P=0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction P=0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH.ConclusionsCSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.

Project description:BackgroundExacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation.MethodsMice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 h of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 min. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 h.ResultsPlatelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia.ConclusionOur findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Dataset Information

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study.

Background

Methods

Results

Conclusion

Publications

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study.

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