Association of Changed Serum Brain Biomarkers With Perihematomal Edema and Early Clinical Outcome in Primary ICH Patients

Background and Purpose: Perihematomal edema (PHE) contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors (GFs) is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with PHE and clinical outcome in ICH patients. Methods: Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated. Noncontrast CT was performed on admission for diagnosis of ICH and quantification of initial hematoma volume. MRI was performed on day 3 in order to evaluate PHE. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor (VEGF) and Angiopoietin-1(Ang-1) on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale (mRS) at 90days. Results: Increased MMP-3 levels were independently associated with PHE volume (P<0.05). Cytotoxic edema (CE) surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. CE did not correlate with the level of any of the biomarkers studied. Levels of MMP-3 ≥12.4 ng/ml and MMP-9 ≥192.4 ng/ml but not VEGF and Ang-1 predicted poor clinical outcome at 90 days (mRS>3) independent of stroke severity and hematoma volume at baseline (OR 25.3, P=0.035; OR 68.9, P=0.023; respectively). Conclusion: Metalloproteinases 3 and 9 seem to be significantly involved in secondary brain injury and outcome after primary ICH in humans and thus should be further evaluated as targets for therapeutic strategies in this devastating disorder.

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Perihematomal Diffusion Restriction in Intracerebral Hemorrhage Depends on Hematoma Volume, But Does Not Predict Outcome

Cerebrovascular Diseases ◽

10.1159/000446549 ◽

2016 ◽

Vol 42 (3-4) ◽

pp. 280-287 ◽

Cited By ~ 3

Author(s):

Sebastian Stösser ◽

Hermann Neugebauer ◽

Katharina Althaus ◽

Albert C. Ludolph ◽

Jan Kassubek ◽

...

Keyword(s):

Clinical Outcome ◽

Intracerebral Hemorrhage ◽

Symptom Onset ◽

Independent Predictor ◽

Severe Disability ◽

Clinical Predictors ◽

Hematoma Volume ◽

Diffusion Restriction ◽

Apparent Diffusion ◽

Perihematomal Edema

Background: Perihematomal diffusion restriction (PDR) is a frequent finding in primary intracerebral hemorrhage (ICH) on diffusion-weighted MRI. Its frequency, associated clinical and imaging findings and impact on clinical outcome are not well understood. Methods: This is a retrospective single-center analysis of 172 patients with primary ICH who received MRI within 24 h from symptom onset. PDR was defined as a reduction of apparent diffusion coefficient below 550 × 10-6 mm2/s. Multivariate regression analyses were used to assess independent imaging and clinical predictors of PDR. Clinical outcome was assessed using the modified Rankin scale (mRS) at discharge. Results: PDR was present in 88 patients (51.2%). Median PDR volume was 1.1 ml (interquartile range 0.2-4.2). Multivariate analyses identified hematoma volume as the key independent predictor of PDR. The volume of perihematomal edema, lobar hematoma location and low diastolic blood pressure at admission were further predictors. Although the occurrence of PDR correlated with in-hospital mortality (75.0 vs. 43.4%, p < 0.001) and moderately severe to severe disability or death at discharge (mRS ≥4; 56.4 vs. 27.8%, p = 0.002), PDR was not an independent predictor of clinical outcome. In contrast, hematoma volume, ventricular extension of hemorrhage and higher age independently predicted an adverse clinical outcome. Conclusions: PDR is common after primary ICH within 24 h of symptom onset. Hematoma volume was identified as the key predictor of PDR. Although PDR was associated with mortality and severe disability, this effect was confounded by established risk factors. These results do not support a role of early PDR as prognostic factor after ICH independent of hematoma volume.

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Association of Microglia/macrophage Polarization With Perihematomal Edema and Clinical Outcome in Patients With Acute Intracerebral Hemorrhage

10.21203/rs.3.rs-318505/v1 ◽

2021 ◽

Author(s):

Xue-Ming Shen ◽

Xiu-Peng Han ◽

Hong-Qi Xu ◽

Yan-Jun Tang ◽

Song Han ◽

...

Keyword(s):

Clinical Outcome ◽

Intracerebral Hemorrhage ◽

Clinical Outcomes ◽

Macrophage Activation ◽

Macrophage Polarization ◽

Treatment Decision ◽

Wilcoxon Test ◽

M1 Phenotype ◽

Perihematomal Edema ◽

M2 Phenotype

Abstract Background: Perihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH) and is associated with poor clinical outcomes. Microglial and macrophage activation, or their polarization could lead to a pro-inflammatory or anti-inflammatory response in stroke. However, little is known about the association between inflammatory cells and ICH. Thus, we characterized the inflammatory cell response, and assessed its association with parameters such as hematoma, PHE volume, and clinical outcome in patients with acute ICH.Methods: Fifty-two patients with acute ICH were retrospectively enrolled in our study. All patients underwent surgery, and brain tissue from the PHE was acquired. Immunofluorescence staining was performed to evaluate microglia (CD11b+/TMEM119+), macrophages (CD11b+/TMEM119-), and the M1 (MHC+/CD11b+) and M2 (CD206+/CD11b+) phenotypes. The relative PHE (r-PHE) was the main marker for assessing PHE volume. The Wilcoxon test and Spearman correlation analysis were the main statistical analysis methods used.Results: Microglia/macrophages, and their phenotypes were detected within 6 hours after stroke. Microglia and the M2 phenotype were negatively correlated with r-PHE, while macrophages and the M1 phenotype were positively correlated with r-PHE; however, these parameters were not associated with age, sex, or location. There was a positive correlation between the microglia and M2-phenotype levels (r = 0.443, p = 0.001) and between the macrophage and M1-phenotype levels (r = 0.458, p <0.001). Microglia (r = -0.295, p = 0.033) and M2-phenotype (r = -0.384, p = 0.005) levels were negatively correlated with the National Institutes of Health stroke scale (NIHSS) after treatment.Finally, using lasso Poisson regression models, we developed a score for predicting the NIHSS score after treatment. Decision curve analysis showed notable net benefits of this score.Conclusion: Microglial and macrophage activation, and their polarization were significantly associated with r-PHE and clinical outcomes in ICH, and could provide therapeutic insights for PHE management after hemorrhagic stroke.

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