Inflammation of central nervous system fiber tracts is active in patients over six months post-intracerebral hemorrhage

The occurrence and extent of central nervous system (CNS) fiber tract inflammation in chronic-phase intracerebral hemorrhage (ICH) patients are not well understood due to the heterogeneity of Wallerian degeneration (WD). This study aims to investigate the presence of CNS fiber tract inflammation in chronic-phase ICH patients and to characterize any inflammatory cells in the fiber tract. An in vivo translocator protein (TSPO)-PET study was undertaken in 22 ICH patients over 6 months after stroke who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Twenty-three healthy controls or participants with various CNS diseases were included. Cerebral peduncle (CP) TSPO uptake was calculated as the average standardized uptake value ratio (SUVr). To aid interpretation of the TSPO uptake results at the CNS fiber tract level, spatial transcriptome sequencing was used to identify fiber tract inflammation in an ICH mouse model at 4wks post-onset and to characterize the cells present in the inflamed fiber tract. PET imaging showed that CP TSPO SUVr values in patients over 6 months since ICH were higher than in healthy controls (mean CP SUVr ± SD; ICH: 1.19 ± 0.11; control: 1.02 ± 0.08; P < 0.0001), and there was an obvious negative correlation between CP TSPO uptake and CP volume, which means that the CNS fiber tract inflammation persists and is still active in chronic-phase ICH patients, which may worsen their prognosis. Spatial transcriptome sequencing of the CNS fiber tract in ICH model mice identified a population of peripheral-derived pro-inflammatory macrophages contributing to the increased TSPO uptake. CP uptake was associated with frontal bone marrow uptake according to association analyses, indicating the cells possibly extending from the skull bone marrow into CNS in the chronic phase.