Cargando…

Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation

Background: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the cap...

Descripción completa

Detalles Bibliográficos
Autores principales: Slevin, Mark, García-Lara, Elisa, Capitanescu, Bogdan, Sanfeliu, Coral, Zeinolabediny, Yasmin, AlBaradie, Raid, Olah, Peter, Guo, Baoqiang, Pirici, Daniel, Di Napoli, Mario, Popa-Wagner, Aurel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563733/
https://www.ncbi.nlm.nih.gov/pubmed/32971821
http://dx.doi.org/10.3390/jcm9093053
_version_ 1783595554037563392
author Slevin, Mark
García-Lara, Elisa
Capitanescu, Bogdan
Sanfeliu, Coral
Zeinolabediny, Yasmin
AlBaradie, Raid
Olah, Peter
Guo, Baoqiang
Pirici, Daniel
Di Napoli, Mario
Popa-Wagner, Aurel
author_facet Slevin, Mark
García-Lara, Elisa
Capitanescu, Bogdan
Sanfeliu, Coral
Zeinolabediny, Yasmin
AlBaradie, Raid
Olah, Peter
Guo, Baoqiang
Pirici, Daniel
Di Napoli, Mario
Popa-Wagner, Aurel
author_sort Slevin, Mark
collection PubMed
description Background: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel to or appear at other locations within the brain that might account for later chronic neuroinflammatory or neurodegenerative effects. Methods: Immunohistochemistry was performed on Formalin-fixed, paraffin-embedded archived brain tissue blocks obtained at autopsy from stroke patients and age-matched controls. We modelled mCRP migration into the brain after haemorrhagic stroke by infusing mCRP (3.5 µg) into the hippocampus of mice and localized mCRP with histological and immunohistochemistry methods. Results: On human tissue in the early stages of haemorrhage, there was no staining of mCRP. However, with increasing post-stroke survival time, mCRP immunostaining was associated with some parenchymal brain cells, some stroke-affected neurons in the surrounding areas and the lumen of large blood vessels as well as brain capillaries. Further from the peri-haematoma region, however, mCRP was detected in the lumen of micro-vessels expressing aquaporin 4 (AQP4). In the hypothalamus, we detected clusters of neurons loaded with mCRP along with scattered lipofuscin-like deposits. In the peri-haematoma region of patients, mCRP was abundantly seen adjacent to AQP4 immunoreactivity. When we stereotactically injected mCRP into the hippocampus of mice, we also observed strong expression in distant neurones of the hypothalamus as well as cortical capillaries. Conclusions: mCRP is abundantly expressed in the brain after haemorrhagic stroke, directly impacting the pathophysiological development of the haematoma. In addition, it may have indirect effects, where the microcirculatory system appears to be able to carry it throughout the cortex as far as the hypothalamus, allowing for long-distance effects and damage through its capacity to induce inflammation and degenerate neuronal perivascular compartments.
format Online
Article
Text
id pubmed-7563733
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75637332020-10-27 Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation Slevin, Mark García-Lara, Elisa Capitanescu, Bogdan Sanfeliu, Coral Zeinolabediny, Yasmin AlBaradie, Raid Olah, Peter Guo, Baoqiang Pirici, Daniel Di Napoli, Mario Popa-Wagner, Aurel J Clin Med Article Background: We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel to or appear at other locations within the brain that might account for later chronic neuroinflammatory or neurodegenerative effects. Methods: Immunohistochemistry was performed on Formalin-fixed, paraffin-embedded archived brain tissue blocks obtained at autopsy from stroke patients and age-matched controls. We modelled mCRP migration into the brain after haemorrhagic stroke by infusing mCRP (3.5 µg) into the hippocampus of mice and localized mCRP with histological and immunohistochemistry methods. Results: On human tissue in the early stages of haemorrhage, there was no staining of mCRP. However, with increasing post-stroke survival time, mCRP immunostaining was associated with some parenchymal brain cells, some stroke-affected neurons in the surrounding areas and the lumen of large blood vessels as well as brain capillaries. Further from the peri-haematoma region, however, mCRP was detected in the lumen of micro-vessels expressing aquaporin 4 (AQP4). In the hypothalamus, we detected clusters of neurons loaded with mCRP along with scattered lipofuscin-like deposits. In the peri-haematoma region of patients, mCRP was abundantly seen adjacent to AQP4 immunoreactivity. When we stereotactically injected mCRP into the hippocampus of mice, we also observed strong expression in distant neurones of the hypothalamus as well as cortical capillaries. Conclusions: mCRP is abundantly expressed in the brain after haemorrhagic stroke, directly impacting the pathophysiological development of the haematoma. In addition, it may have indirect effects, where the microcirculatory system appears to be able to carry it throughout the cortex as far as the hypothalamus, allowing for long-distance effects and damage through its capacity to induce inflammation and degenerate neuronal perivascular compartments. MDPI 2020-09-22 /pmc/articles/PMC7563733/ /pubmed/32971821 http://dx.doi.org/10.3390/jcm9093053 Text en © 2020 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Slevin, Mark
García-Lara, Elisa
Capitanescu, Bogdan
Sanfeliu, Coral
Zeinolabediny, Yasmin
AlBaradie, Raid
Olah, Peter
Guo, Baoqiang
Pirici, Daniel
Di Napoli, Mario
Popa-Wagner, Aurel
Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title_full Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title_fullStr Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title_full_unstemmed Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title_short Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation
title_sort monomeric c-reactive protein aggravates secondary degeneration after intracerebral haemorrhagic stroke and may function as a sensor for systemic inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563733/
https://www.ncbi.nlm.nih.gov/pubmed/32971821
http://dx.doi.org/10.3390/jcm9093053
work_keys_str_mv AT slevinmark monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT garcialaraelisa monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT capitanescubogdan monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT sanfeliucoral monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT zeinolabedinyyasmin monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT albaradieraid monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT olahpeter monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT guobaoqiang monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT piricidaniel monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT dinapolimario monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation
AT popawagneraurel monomericcreactiveproteinaggravatessecondarydegenerationafterintracerebralhaemorrhagicstrokeandmayfunctionasasensorforsystemicinflammation