Affiliation:
1. Neurology, McGovern Med Sch at UT Health, Houston, TX
2. Neuroscience, Kaiser Permanente, Redwood City, CA
Abstract
Introduction:
Intracerebral hemorrhage (ICH) dramatically remodels the blood-brain barrier (BBB). However, BBB remodeling may differ between ICH cases due to location (lobar or deep hemorrhage) as well as etiology (hypertension, trauma or amyloid-β). This study addresses whether serum levels of BBB remodeling proteins, including matrix metalloproteases (MMPs), transforming growth factor-β (TGF-β) and fibronectin (FN), are biomarkers of ICH etiology and outcomes.
Hypothesis:
We hypothesize that serum MMP, TGF-β and FN levels are predictive of ICH etiology, severity and functional outcomes.
Methods:
Patient data (n=37 lobar, n=42 deep ICH patients) were abstracted from prospective ICH databases detailing admission data, radiology, hospital course (ICH score, NIH stroke scale [NIHSS], Glasgow Coma Scale [GCS]), and functional outcomes (modified Rankin Scale [mRS], Euroqol). Serum samples were drawn from admission to 10 days post-injury. Levels of TGF-β isoforms, MMPs and FN were measured by multiplex ELISA (11 cytokines total) and divided into early (<24hrs-5 days) and late (6-10 days) groups for analysis. P-values were obtained by Spearman correlation, Wilcoxon rank sum or Kruskal Wallis tests, with false discovery rate controlled at 0.05.
Results:
Early FN levels were lower in lobar than deep hemorrhages (
p=0.007
). Levels of early MMP-8, -9 and -10, as well as levels of TGF-β1, TGF-β2 and TGF–β3 positively correlated with initial neurological deficits (NIHSS,
p=0.005-0.039
). Additionally, late MMP-8 levels negatively correlated with edema (
p=0.018
). Furthermore, early MMP-1, TGF-β1 and TGF-β3 levels positively correlated with persistent neurologic deficits (mRS) at discharge and 90-days post-injury (
p=0.003-0.041
). Finally, females had lower early levels of MMP-8, -9 and -10 than males (
p=0.019, 0.019, 0.019
).
Conclusion:
BBB remodeling markers change with ICH location and patient sex, and are predictive of functional deficits and recovery. Specifically, these markers correlate with
(1)
the type and severity of initial injury,
(2)
the induction of secondary injury and
(3)
long-term functional recovery. This research improves our understanding of BBB responses to ICH, and may lead to novel biomarkers for ICH diagnosis and treatment.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)