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Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology

Long pentraxin PTX3, a pattern recognition molecule involved in innate immune responses, is upregulated by pro-inflammatory stimuli, contributors to secondary damage in traumatic brain injury (TBI). We analyzed PTX3 involvement in mice subjected to controlled cortical impact, a clinically relevant T...

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Autores principales: Oggioni, Marco, Mercurio, Domenico, Minuta, Denise, Fumagalli, Stefano, Popiolek-Barczyk, Katarzyna, Sironi, Marina, Ciechanowska, Agata, Ippati, Stefania, De Blasio, Daiana, Perego, Carlo, Mika, Joanna, Garlanda, Cecilia, De Simoni, Maria-Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100171/
https://www.ncbi.nlm.nih.gov/pubmed/33953334
http://dx.doi.org/10.1038/s41598-021-89032-7
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author Oggioni, Marco
Mercurio, Domenico
Minuta, Denise
Fumagalli, Stefano
Popiolek-Barczyk, Katarzyna
Sironi, Marina
Ciechanowska, Agata
Ippati, Stefania
De Blasio, Daiana
Perego, Carlo
Mika, Joanna
Garlanda, Cecilia
De Simoni, Maria-Grazia
author_facet Oggioni, Marco
Mercurio, Domenico
Minuta, Denise
Fumagalli, Stefano
Popiolek-Barczyk, Katarzyna
Sironi, Marina
Ciechanowska, Agata
Ippati, Stefania
De Blasio, Daiana
Perego, Carlo
Mika, Joanna
Garlanda, Cecilia
De Simoni, Maria-Grazia
author_sort Oggioni, Marco
collection PubMed
description Long pentraxin PTX3, a pattern recognition molecule involved in innate immune responses, is upregulated by pro-inflammatory stimuli, contributors to secondary damage in traumatic brain injury (TBI). We analyzed PTX3 involvement in mice subjected to controlled cortical impact, a clinically relevant TBI mouse model. We measured PTX3 mRNA and protein in the brain and its circulating levels at different time point post-injury, and assessed behavioral deficits and brain damage progression in PTX3 KO mice. PTX3 circulating levels significantly increased 1–3 weeks after injury. In the brain, PTX3 mRNA was upregulated in different brain areas starting from 24 h and up to 5 weeks post-injury. PTX3 protein significantly increased in the brain cortex up to 3 weeks post-injury. Immunohistochemical analysis showed that, 48 h after TBI, PTX3 was localized in proximity of neutrophils, likely on neutrophils extracellular traps (NETs), while 1- and 2- weeks post-injury PTX3 co-localized with fibrin deposits. Genetic depletion of PTX3 did not affect sensorimotor deficits up to 5 weeks post-injury. At this time-point lesion volume and neuronal count, axonal damage, collagen deposition, astrogliosis, microglia activation and phagocytosis were not different in KO compared to WT mice. Members of the long pentraxin family, neuronal pentraxin 1 (nPTX1) and pentraxin 4 (PTX4) were also over-expressed in the traumatized brain, but not neuronal pentraxin 2 (nPTX2) or short pentraxins C-reactive protein (CRP) and serum amyloid P-component (SAP). The long-lasting pattern of activation of PTX3 in brain and blood supports its specific involvement in TBI. The lack of a clear-cut phenotype in PTX3 KO mice may depend on the different roles of this protein, possibly involved in inflammation early after injury and in repair processes later on, suggesting distinct functions in acute phases versus sub-acute or chronic phases. Brain long pentraxins, such as PTX4—shown here to be overexpressed in the brain after TBI—may compensate for PTX3 absence.
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spelling pubmed-81001712021-05-07 Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology Oggioni, Marco Mercurio, Domenico Minuta, Denise Fumagalli, Stefano Popiolek-Barczyk, Katarzyna Sironi, Marina Ciechanowska, Agata Ippati, Stefania De Blasio, Daiana Perego, Carlo Mika, Joanna Garlanda, Cecilia De Simoni, Maria-Grazia Sci Rep Article Long pentraxin PTX3, a pattern recognition molecule involved in innate immune responses, is upregulated by pro-inflammatory stimuli, contributors to secondary damage in traumatic brain injury (TBI). We analyzed PTX3 involvement in mice subjected to controlled cortical impact, a clinically relevant TBI mouse model. We measured PTX3 mRNA and protein in the brain and its circulating levels at different time point post-injury, and assessed behavioral deficits and brain damage progression in PTX3 KO mice. PTX3 circulating levels significantly increased 1–3 weeks after injury. In the brain, PTX3 mRNA was upregulated in different brain areas starting from 24 h and up to 5 weeks post-injury. PTX3 protein significantly increased in the brain cortex up to 3 weeks post-injury. Immunohistochemical analysis showed that, 48 h after TBI, PTX3 was localized in proximity of neutrophils, likely on neutrophils extracellular traps (NETs), while 1- and 2- weeks post-injury PTX3 co-localized with fibrin deposits. Genetic depletion of PTX3 did not affect sensorimotor deficits up to 5 weeks post-injury. At this time-point lesion volume and neuronal count, axonal damage, collagen deposition, astrogliosis, microglia activation and phagocytosis were not different in KO compared to WT mice. Members of the long pentraxin family, neuronal pentraxin 1 (nPTX1) and pentraxin 4 (PTX4) were also over-expressed in the traumatized brain, but not neuronal pentraxin 2 (nPTX2) or short pentraxins C-reactive protein (CRP) and serum amyloid P-component (SAP). The long-lasting pattern of activation of PTX3 in brain and blood supports its specific involvement in TBI. The lack of a clear-cut phenotype in PTX3 KO mice may depend on the different roles of this protein, possibly involved in inflammation early after injury and in repair processes later on, suggesting distinct functions in acute phases versus sub-acute or chronic phases. Brain long pentraxins, such as PTX4—shown here to be overexpressed in the brain after TBI—may compensate for PTX3 absence. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8100171/ /pubmed/33953334 http://dx.doi.org/10.1038/s41598-021-89032-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Oggioni, Marco
Mercurio, Domenico
Minuta, Denise
Fumagalli, Stefano
Popiolek-Barczyk, Katarzyna
Sironi, Marina
Ciechanowska, Agata
Ippati, Stefania
De Blasio, Daiana
Perego, Carlo
Mika, Joanna
Garlanda, Cecilia
De Simoni, Maria-Grazia
Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title_full Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title_fullStr Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title_full_unstemmed Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title_short Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
title_sort long pentraxin ptx3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100171/
https://www.ncbi.nlm.nih.gov/pubmed/33953334
http://dx.doi.org/10.1038/s41598-021-89032-7
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