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Rapid neuroinflammatory changes in human acute intracerebral haemorrhage

Rapid neuroinflammatory changes in human acute intracerebral haemorrhage
Rapid neuroinflammatory changes in human acute intracerebral haemorrhage
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.
Spontaneous intracerebral haemorrhage, Lobar, Microglia, Morphology
1465-1479
Shtaya, Anan
7b9d3363-83f4-41a9-ae6d-3de05cabb937
Bridges, Leslie R.
2d3571a7-b0fd-47c2-b7ab-8abd7daa6f8e
Esiri, Margaret M.
35d44a22-0684-4f9e-8c46-1d948c63a502
Lam-Wong, Joanne
d6e686f4-0546-44a5-aa12-0958b14b3be3
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Hainsworth, Atticus H.
221ee2c3-0802-46a2-9da2-07a4b6e3e7b2
Shtaya, Anan
7b9d3363-83f4-41a9-ae6d-3de05cabb937
Bridges, Leslie R.
2d3571a7-b0fd-47c2-b7ab-8abd7daa6f8e
Esiri, Margaret M.
35d44a22-0684-4f9e-8c46-1d948c63a502
Lam-Wong, Joanne
d6e686f4-0546-44a5-aa12-0958b14b3be3
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Hainsworth, Atticus H.
221ee2c3-0802-46a2-9da2-07a4b6e3e7b2

Shtaya, Anan, Bridges, Leslie R., Esiri, Margaret M., Lam-Wong, Joanne, Nicoll, James A.R., Boche, Delphine and Hainsworth, Atticus H. (2019) Rapid neuroinflammatory changes in human acute intracerebral haemorrhage. Annals of Clinical and Translational Neurology, 6 (8), 1465-1479. (doi:10.1002/acn3.50842).

Record type: Article

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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Accepted/In Press date: 25 June 2019
e-pub ahead of print date: 13 July 2019
Published date: August 2019
Keywords: Spontaneous intracerebral haemorrhage, Lobar, Microglia, Morphology

Identifiers

Local EPrints ID: 432110
URI: http://eprints.soton.ac.uk/id/eprint/432110
PURE UUID: da4ca03a-c62b-422c-8d0e-aa1e6a901376
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 02 Jul 2019 16:30
Last modified: 26 Nov 2021 02:45

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Contributors

Author: Anan Shtaya
Author: Leslie R. Bridges
Author: Margaret M. Esiri
Author: Joanne Lam-Wong
Author: Delphine Boche ORCID iD
Author: Atticus H. Hainsworth

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