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Rapid neuroinflammatory changes in human acute intracerebral hemorrhage

Shtaya, A; Bridges, LR; Esiri, MM; Lam-Wong, J; Nicoll, JAR; Boche, D; Hainsworth, AH (2019) Rapid neuroinflammatory changes in human acute intracerebral hemorrhage. Annals of Clinical and Translational Neurology, 6 (8). pp. 1465-1479. ISSN 2328-9503 https://doi.org/10.1002/acn3.50842
SGUL Authors: Hainsworth, Atticus Henry Shtaya, Anan BY

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Abstract

Objective 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. Methods 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. Results 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. 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.

Item Type: Article
Additional Information: © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Annals of Clinical and Translational Neurology
ISSN: 2328-9503
Dates:
DateEvent
11 August 2019Published
13 July 2019Published Online
25 June 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
10717-19St George's University of LondonUNSPECIFIED
UNSPECIFIEDNational Institute for Health ResearchUNSPECIFIED
URI: https://openaccess.sgul.ac.uk/id/eprint/110965
Publisher's version: https://doi.org/10.1002/acn3.50842

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