Hydrocephalus Induced by Intraventricular Peroxiredoxin-2: The Role of Macrophages in the Choroid Plexus.

Abstract

The choroid plexus (CP) is the primary source of cerebrospinal fluid in the central nervous system. Recent evidence indicates that inflammatory pathways at the CP may be involved in hydrocephalus development. Peroxiredoxin 2 (Prx2) is a major component of red blood cells. Extracellular Prx2 is proinflammatory, and its release after red blood cell lysis may contribute to hydrocephalus after intraventricular hemorrhage. This study aimed to identify alterations in CP macrophages and dendritic cells following intracerebroventricular Prx2 injection and investigate the relationship between macrophages/dendritic cells and hydrocephalus. There were two parts to this study. In the first part, adult male Sprague-Dawley rats received an intracerebroventricular injection of Prx2 or saline. In the second part, Prx2 was co-injected with clodronate liposomes or control liposomes. All animals were euthanized at 24 h after magnetic resonance imaging. Immunohistochemistry was used to evaluate macrophages in CP, magnetic resonance imaging to quantify hydrocephalus, and histology to assess ventricular wall damage. The intracerebroventricular injection of Prx2 not only increased the OX-6 positive cells, but it also altered their location in the CP and immunophenotype. Co-injecting clodronate liposomes with Prx2 decreased the number of macrophages and simultaneously attenuated Prx2-induced hydrocephalus and ventricular wall damage. These results suggest that CP macrophages play an essential role in CP inflammation-induced hydrocephalus. These macrophages may be a potential therapeutic target in post-hemorrhagic hydrocephalus.

• Authors: Ting Chen, Xiaoxiao Tan, Fan Xia, Ya Hua, Richard F Keep, Guohua Xi
• Journal: Biomolecules (Biomolecules) Vol. 11 Issue 5 (04 29 2021) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 33946699 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Liposomes
• OX-6 monoclonal antibody
• Clodronic Acid
• Peroxiredoxins

Topics

• Animals
• Antibodies, Monoclonal (metabolism)
• Choroid Plexus (immunology)
• Clodronic Acid (administration & dosage)
• Disease Models, Animal
• Hydrocephalus (chemically induced, immunology, pathology)
• Infusions, Intraventricular
• Liposomes
• Macrophages (metabolism)
• Magnetic Resonance Imaging
• Male
• Peroxiredoxins (adverse effects)
• Rats
• Rats, Sprague-Dawley