Rapid neuroinflammatory changes in human acute intracerebral haemorrhage

Abstract

Objective: spontaneous intracerebral haemorrhage (ICH) is the commonest form of haemorrhagic stroke and is associated with a poor prognosis. Neurosurgical removal of intracerebral haematoma 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.

Methods: we studied histological changes in post-mortem 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.

Results: peri-haematoma, the observed ICH-related changes include oedema, tissue neutrophils and macrophages from day 1. Ischaemic neurons and swollen endothelial cells were common at day 1 and universal after day 5, as were intra-mural erythrocytes within small vessel walls. Activated microglia were evident at day 1 post-ICH. There was a significant increase of Iba1 positive area fraction at 0-2 (3-fold), 3-5 (4-fold) and 7-12 days post ICH (9-fold) relative to controls. Giant microglia were detected peri-haematoma from day 5 and consistently 7-12 days post ICH.

Interpretation: 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.

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Identifiers

ORCID for James A.R. Nicoll: orcid.org/0000-0002-9444-7246

ORCID for Delphine Boche: orcid.org/0000-0002-5884-130X

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