Neuroinflammation and blood-brain barrier breakdown in acute, clinical intracerebral hemorrhage
O Jones, Saffwan Mohamed, Rainer Hinz, Alastair Paterson, Oluwaseun A. Sobowale, Ben Dickie, Laura M. Parkes, Adrian Parry‐Jones
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 [ 11 C]( 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 ND were 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 .