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

Abstract

Background: Perihematomal edema (PHE) following primary intracranial hemorrhages (ICHs) affects the patient outcome. Also, serum biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) have been associated with ICHs outcome. We aimed to investigate the association between these biomarkers and PHE in ICH patients. Methods:In this cross-sectional study, patients with primary ICH between January 2020 and August 2020 were evaluated. All participants underwent spiral brain computed tomography scans upon admission, and 48 to 72 hours later and quantification of initial hematoma volume was performed. Serum level of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), GFAP, and S100B on admission were measured by enzyme-linked immunosorbent assays. Acute clinical outcome was assessed by the modified-Rankin scale, National Institute of Health Stroke Scale (NIHSS), and ICH score.Results: Thirty-seven ICH patients (21 patients with a favorable outcome and 16 unfavorable) were studied. Compared with survival patients, nonsurvivor patients showed a higher serum level of MMP-9, VEGF, GFAP, and S100B (P < 0.05). Scores of absolute PHE, edema expansion distance, and PHE growth rate in the nonsurvivor group were higher than the survivors (P < 0.001). The regression model revealed that MMP-9, VEGF, ICH score, and hematoma volume were associated with the PHE growth rate. S100B and ICH score were associated with edema expansion distance.Conclusions: Our data showed that the serum level of molecular biomarkers was associated with higher PHE volume and PHE scores were higher in nonsurvival patients, suggesting it may have a pathogenic role in developing PHE after ICH.

Immune‐mediated disruption of the blood–brain barrier after intracerebral hemorrhage: Insights and potential therapeutic targets

“…These immune responses and MMP activity further exacerbate BBB disruption and tissue damage. Previous findings have indicated increased MMP‐9 levels in peripheral blood are associated with hematoma enlargement, poor functional prognosis, and increased PHE growth in patients 102 . Inhibiting MMP‐9 can increase the expression of TJPs and basal protein 40 .…”

“…Previous findings have indicated increased MMP‐9 levels in peripheral blood are associated with hematoma enlargement, poor functional prognosis, and increased PHE growth in patients. 102 Inhibiting MMP‐9 can increase the expression of TJPs and basal protein. 40 However, some studies have suggested that MMP‐9 activation may not be a contributing factor to the neurological outcomes in hypertension‐induced ICH.…”

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

“…There is also evidence that thrombin can directly disrupt the BBB by increasing the expression of MMPs and AQP4 in vitro and in vivo [ 43 , 44 ]. Although it is a double-edged sword, VEGF may also tend to aggravate the vasogenic edema in the early stage of ICH [ 45 , 46 ]. Additional evidence has indicated that thrombin can promote the release of vascular endothelial growth factor (VEGF) from astrocytes through the PAR-1/p44/42 mitogen-activated protein kinase (MAPK) pathway [ 47 ], suggesting that thrombin can also increase vascular permeability and subsequently promote the evolution of PHE by inducing VEGF overexpression.…”