Cargando…

Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture

Traumatic brain injury (TBI) represents a major cause of death and disability in early adulthood. Concomitant extracranial injury such as long bone fracture was reported to exacerbate TBI pathology. However, early reciprocal effects and mechanisms have been barely investigated. To address this issue...

Descripción completa

Detalles Bibliográficos
Autores principales: Ritter, Katharina, Jung, Kirsten, Dolderer, Christopher, Appel, Dominik, Oswald, Christine C., Ritz, Ulrike, Schäfer, Michael K. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834824/
https://www.ncbi.nlm.nih.gov/pubmed/33531878
http://dx.doi.org/10.1155/2021/8835730
_version_ 1783642372023779328
author Ritter, Katharina
Jung, Kirsten
Dolderer, Christopher
Appel, Dominik
Oswald, Christine C.
Ritz, Ulrike
Schäfer, Michael K. E.
author_facet Ritter, Katharina
Jung, Kirsten
Dolderer, Christopher
Appel, Dominik
Oswald, Christine C.
Ritz, Ulrike
Schäfer, Michael K. E.
author_sort Ritter, Katharina
collection PubMed
description Traumatic brain injury (TBI) represents a major cause of death and disability in early adulthood. Concomitant extracranial injury such as long bone fracture was reported to exacerbate TBI pathology. However, early reciprocal effects and mechanisms have been barely investigated. To address this issue, C57BL/6N mice were subjected to either the controlled cortical impact (CCI) model of TBI, fracture of the left femur (FF), combined injury (CCI+FF), or sham procedure. Behavioral alterations were monitored until 5 days post injury (dpi), followed by (immuno-)histology, gene and protein expression analyses using quantitative PCR, western blot, and ELISA. We found that CCI+FF mice exhibited increased neurological impairments, reduced recovery, and altered anxiety-related behavior compared to single injury groups. At 5 dpi, cerebral lesion size was not affected by combined injury but exaggerated hippocampal substance loss and increased perilesional astrogliosis were observed in CCI+FF mice compared to isolated CCI. Bone gene expression of the osteogenic markers Runx2, osteocalcin, alkaline phosphatase, and bone sialoprotein was induced by fracture injury but attenuated by concomitant TBI. Plasma concentrations of the biomarkers osteopontin and progranulin were elevated in CCI+FF mice compared to other experimental groups. Taken together, using a murine model of TBI and femoral fracture, we report early reciprocal impairments of brain tissue maintenance, behavioral recovery, and bone repair gene expression. Increased circulating levels of the biomarkers osteopontin and progranulin indicate ongoing tissue inflammation and repair. Our results may have implications for future therapeutic approaches to interfere with the pathological crosstalk between TBI and concomitant bone fracture.
format Online
Article
Text
id pubmed-7834824
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-78348242021-02-01 Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture Ritter, Katharina Jung, Kirsten Dolderer, Christopher Appel, Dominik Oswald, Christine C. Ritz, Ulrike Schäfer, Michael K. E. Mediators Inflamm Research Article Traumatic brain injury (TBI) represents a major cause of death and disability in early adulthood. Concomitant extracranial injury such as long bone fracture was reported to exacerbate TBI pathology. However, early reciprocal effects and mechanisms have been barely investigated. To address this issue, C57BL/6N mice were subjected to either the controlled cortical impact (CCI) model of TBI, fracture of the left femur (FF), combined injury (CCI+FF), or sham procedure. Behavioral alterations were monitored until 5 days post injury (dpi), followed by (immuno-)histology, gene and protein expression analyses using quantitative PCR, western blot, and ELISA. We found that CCI+FF mice exhibited increased neurological impairments, reduced recovery, and altered anxiety-related behavior compared to single injury groups. At 5 dpi, cerebral lesion size was not affected by combined injury but exaggerated hippocampal substance loss and increased perilesional astrogliosis were observed in CCI+FF mice compared to isolated CCI. Bone gene expression of the osteogenic markers Runx2, osteocalcin, alkaline phosphatase, and bone sialoprotein was induced by fracture injury but attenuated by concomitant TBI. Plasma concentrations of the biomarkers osteopontin and progranulin were elevated in CCI+FF mice compared to other experimental groups. Taken together, using a murine model of TBI and femoral fracture, we report early reciprocal impairments of brain tissue maintenance, behavioral recovery, and bone repair gene expression. Increased circulating levels of the biomarkers osteopontin and progranulin indicate ongoing tissue inflammation and repair. Our results may have implications for future therapeutic approaches to interfere with the pathological crosstalk between TBI and concomitant bone fracture. Hindawi 2021-01-18 /pmc/articles/PMC7834824/ /pubmed/33531878 http://dx.doi.org/10.1155/2021/8835730 Text en Copyright © 2021 Katharina Ritter et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ritter, Katharina
Jung, Kirsten
Dolderer, Christopher
Appel, Dominik
Oswald, Christine C.
Ritz, Ulrike
Schäfer, Michael K. E.
Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title_full Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title_fullStr Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title_full_unstemmed Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title_short Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
title_sort early reciprocal effects in a murine model of traumatic brain injury and femoral fracture
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834824/
https://www.ncbi.nlm.nih.gov/pubmed/33531878
http://dx.doi.org/10.1155/2021/8835730
work_keys_str_mv AT ritterkatharina earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT jungkirsten earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT doldererchristopher earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT appeldominik earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT oswaldchristinec earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT ritzulrike earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture
AT schafermichaelke earlyreciprocaleffectsinamurinemodeloftraumaticbraininjuryandfemoralfracture