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

Abstract 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 r...

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Autores principales:	Marco Oggioni, Domenico Mercurio, Denise Minuta, Stefano Fumagalli, Katarzyna Popiolek-Barczyk, Marina Sironi, Agata Ciechanowska, Stefania Ippati, Daiana De Blasio, Carlo Perego, Joanna Mika, Cecilia Garlanda, Maria-Grazia De Simoni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ab84c6e775b8498fa19cd39f64b559e4
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spelling	oai:doaj.org-article:ab84c6e775b8498fa19cd39f64b559e42021-12-02T14:29:03ZLong pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology10.1038/s41598-021-89032-72045-2322https://doaj.org/article/ab84c6e775b8498fa19cd39f64b559e42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89032-7https://doaj.org/toc/2045-2322Abstract 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.Marco OggioniDomenico MercurioDenise MinutaStefano FumagalliKatarzyna Popiolek-BarczykMarina SironiAgata CiechanowskaStefania IppatiDaiana De BlasioCarlo PeregoJoanna MikaCecilia GarlandaMaria-Grazia De SimoniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marco Oggioni Domenico Mercurio Denise Minuta Stefano Fumagalli Katarzyna Popiolek-Barczyk Marina Sironi Agata Ciechanowska Stefania Ippati Daiana De Blasio Carlo Perego Joanna Mika Cecilia Garlanda Maria-Grazia De Simoni Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
description	Abstract 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.
format	article
author	Marco Oggioni Domenico Mercurio Denise Minuta Stefano Fumagalli Katarzyna Popiolek-Barczyk Marina Sironi Agata Ciechanowska Stefania Ippati Daiana De Blasio Carlo Perego Joanna Mika Cecilia Garlanda Maria-Grazia De Simoni
author_facet	Marco Oggioni Domenico Mercurio Denise Minuta Stefano Fumagalli Katarzyna Popiolek-Barczyk Marina Sironi Agata Ciechanowska Stefania Ippati Daiana De Blasio Carlo Perego Joanna Mika Cecilia Garlanda Maria-Grazia De Simoni
author_sort	Marco Oggioni
title	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_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_sort	long pentraxin ptx3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ab84c6e775b8498fa19cd39f64b559e4
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Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology

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