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Article

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

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Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Chester Street, Manchester M15 6BH, UK
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The University of Medicine, Pharmacy, Science and Technology at Targu Mures, 540142 Targu Mures, Romania
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Institut d’Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS and CIBERESP, 08036 Barcelona, Spain
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Department of Anatomy, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
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Applied Medical Sciences College, Majmaah University, Al Majma’ah 15361, Saudi Arabia
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Regenesol LTD, Number 30 the Green Building, 19 New Wakefield Street, Manchester M1 5NP, UK
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Department of Research Methodology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
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Department of Neurology and Stroke Unit, San Camillo de’ Lellis General Hospital, 02100 Rieti, Italy
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Neurological Section, Neuro-epidemiology Unit, SMDN, Centre for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, 67039 L’Aquila, Italy
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Center of Eexperimental and Clinical Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania
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Griffith University Menzies Health Institute of Queensland, Gold Coast Campus, Gold Coast Campus, QLD 4222, Australia
*
Authors to whom correspondence should be addressed.
Equal contribution.
J. Clin. Med. 2020, 9(9), 3053; https://doi.org/10.3390/jcm9093053
Received: 8 August 2020 / Revised: 15 September 2020 / Accepted: 17 September 2020 / Published: 22 September 2020
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. View Full-Text
Keywords: mCRP; haemorrhagic stroke; neuroinflammation; hypothalamus; micro-circulatory system mCRP; haemorrhagic stroke; neuroinflammation; hypothalamus; micro-circulatory system
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MDPI and ACS Style

Slevin, M.; E, E.G.-L.; Capitanescu, B.; Sanfeliu, C.; Zeinolabediny, Y.; AlBaradie, R.; Olah, P.; Guo, B.; Pirici, D.; Napoli, M.D.; Popa-Wagner, A. Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation. J. Clin. Med. 2020, 9, 3053. https://doi.org/10.3390/jcm9093053

AMA Style

Slevin M, E EG-L, Capitanescu B, Sanfeliu C, Zeinolabediny Y, AlBaradie R, Olah P, Guo B, Pirici D, Napoli MD, Popa-Wagner A. Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation. Journal of Clinical Medicine. 2020; 9(9):3053. https://doi.org/10.3390/jcm9093053

Chicago/Turabian Style

Slevin, Mark, Elisa G.-L. E, Bogdan Capitanescu, Coral Sanfeliu, Yasmin Zeinolabediny, Raid AlBaradie, Peter Olah, Baoqiang Guo, Daniel Pirici, Mario D. Napoli, and Aurel Popa-Wagner. 2020. "Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation" Journal of Clinical Medicine 9, no. 9: 3053. https://doi.org/10.3390/jcm9093053

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