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.
Highlights
The choroid plexuses (CPs) are the primary source of cerebrospinal fluid (CSF), and they play an essential role in maintaining central nervous system (CNS) homeostasis
OX-6 positive (OX-6 (+)) cells were detected in the CP in the saline control group, with most of them located in the CP stroma (Figure 1a)
The main findings of this study were: (a) OX-6 (+) cells are predominately located in the stroma of CP in control rats; (b) in contrast, most of them appeared on the CP apical surface after Peroxiredoxin 2 (Prx2) injection with an increased number; (c) the OX-6(+) cells in CP were reduced when Prx2 was co-injected with clodronate liposomes; (d) co-injecting Prx2 with clodronate liposomes attenuated neutrophil infiltration, hydrocephalus and ventricular wall damage
Summary
The choroid plexuses (CPs) are the primary source of cerebrospinal fluid (CSF), and they play an essential role in maintaining central nervous system (CNS) homeostasis. Peroxiredoxin 2 (Prx2) is a major component of red blood cells (RBCs) [4] It can be released into extracellular space after hemolysis and evoke a series of severe inflammatory responses [5]. Our previous studies revealed that ionized calcium-binding adaptor molecule 1 (Iba-1, a macrophage/microglia marker) positive cells were increased at the CP after subarachnoid hemorrhage and in blood component (thrombin and Prx2)-induced hydrocephalus [6,7]. This suggests that CP resident macrophages may play a role in hydrocephalus development
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