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Peer-reviewed veterinary case report

Neutrophil traps found in spinal fluid and blood of dogs

By Wohlsein, Jan Christian et al.·Published in PloS one·2024·Department of Small Animal Medicine and Surgery, Germany·View original on PubMed

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Original publication title: Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

Species:
dog
Brain & nervesDogs

Plain-English summary

A 5-year-old dog with steroid-responsive meningitis-arteritis (SRMA) was studied to understand how certain immune cells might be causing inflammation in the brain and spinal cord. Researchers found that these cells were forming structures called neutrophil extracellular traps (NETs) in the dog's cerebrospinal fluid during acute illness, but not when the dog was in remission. The study showed that the dog's ability to clear these NETs was reduced when it was sick, which could be contributing to the ongoing inflammation. This research helps explain the immune system's role in SRMA and could lead to better treatments in the future.

People also search for: dog meningitis treatment · SRMA in dogs symptoms · neutrophil extracellular traps in dogs

Abstract

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/38241272/