Neuroinflammation and blood-brain barrier breakdown in acute, clinical intracerebral hemorrhage.

Abstract

Neuroinflammation is a promising therapeutic target in intracerebral hemorrhage (ICH), characterized in the brain by microglial activation and blood-brain barrier (BBB) breakdown. In this study, 36 acute, spontaneous, supratentorial ICH patients underwent dynamic contrast-enhanced MRI to measure BBB permeability (K^trans) 1-3 days post-onset and 16 returned for [¹¹C](R)-PK11195 PET to quantify microglial activation (BP_ND), 2-7 days post-onset. We first tested if these markers were increased and co-localized in the perihematomal brain and found that perihematomal K^trans and BP_ND were increased vs. the contralateral brain, but regions of high K^trans and BP_ND only overlapped by a mean of 4.9%. We then tested for associations of perihematomal K^trans and BP_ND with clinical characteristics (age, ICH volume & location, blood pressure), other markers of inflammation (edema, IL-6, and CRP), and long-term functional outcome (90-day mRS). Lower perihematomal BP_ND was associated with increasing age. Lobar hemorrhage was associated with greater K^trans than deep, but K^trans and BP_ND were not associated with ICH volume, or other inflammatory markers. While perihematomal K^trans and BP_NDwere not associated with outcome, contralateral K^trans was significantly associated with greater 90-day mRS. Exploratory analyses demonstrated that blood pressure variability over 72 h was also associated with contralateral K^trans.