Rapid neuroinflammatory changes in human acute intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is the commonest form of hemorrhagic stroke and is associated with a poor prognosis. Neurosurgical removal of intracerebral hematoma has limited benefit and no pharmacotherapies are available. In acute ICH, primary tissue damage is followed by secondary pathology, where the cellular and neuroinflammatory changes are poorly understood.

We studied histological changes in postmortem tissue from a cohort of spontaneous supra-tentorial primary ICH cases (n = 27) with survival of 1-12 days, compared to a matched control group (n = 16) examined in corresponding regions. Hematoxylin-eosin and microglial (Iba1) immunolabelled sections were assessed at 0-2, 3-5, and 7-12 days post-ICH.

Peri-hematoma, the observed ICH-related changes include edema, tissue neutrophils and macrophages from day 1. Ischemic neurons and swollen endothelial cells were common at day 1 and universal after day 5, as were intramural erythrocytes within small vessel walls. Activated microglia were evident at day 1 post-ICH. There was a significant increase in Iba1 positive area fraction at 0-2 (threefold), 3-5 (fourfold), and 7-12 days post ICH (ninefold) relative to controls. Giant microglia were detected peri-hematoma from day 5 and consistently 7-12 days post-ICH.

Our data indicate that neuroinflammatory processes commence from day 1 post-ICH with changing microglial size and morphology following ICH and up to day 12. From day 5 some microglia exhibit a novel multiply nucleated morphology, which may be related to changing phagocytic function. Understanding the time course of neuroinflammatory changes, post-ICH may reveal novel targets for therapy and brain restoration.