Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many co...

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Main Authors: Guoxiang Xiong, Ian Jean, Anthony M. Farrugia, Hannah Metheny, Brian N. Johnson, Noam A. Cohen, Akiva S. Cohen
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2024.1339262/full
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author Guoxiang Xiong
Ian Jean
Anthony M. Farrugia
Hannah Metheny
Brian N. Johnson
Noam A. Cohen
Noam A. Cohen
Akiva S. Cohen
Akiva S. Cohen
author_facet Guoxiang Xiong
Ian Jean
Anthony M. Farrugia
Hannah Metheny
Brian N. Johnson
Noam A. Cohen
Noam A. Cohen
Akiva S. Cohen
Akiva S. Cohen
author_sort Guoxiang Xiong
collection DOAJ
description Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury. Although not all pathological structures were stained by all markers at all time points, we found damaged neurons and deformed dendrites in gray matter, punctate and perivascular structures in white matter, and axonal blebs and Wallerian degeneration in both gray and white matter. The present study demonstrates the temporal and structural sensitivities of the three biomarkers: each marker is highly effective for a set of pathological structures, each of which in turn emerges at a particular time point. Furthermore, the different biomarkers showed different abilities at detecting identical types of pathological structures. In contrast to previous studies that have used a single biomarker at a single time range, the present report strongly recommends that a combination of different biomarkers should be adopted and different time points need to be checked when assessing neuropathology after TBI.
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spelling doaj.art-5f458d43e26147a79f057fa7b6d967d72024-01-30T04:18:09ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-01-011810.3389/fnins.2024.13392621339262Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouseGuoxiang Xiong0Ian Jean1Anthony M. Farrugia2Hannah Metheny3Brian N. Johnson4Noam A. Cohen5Noam A. Cohen6Akiva S. Cohen7Akiva S. Cohen8Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesPhiladelphia Veterans Affairs Medical Center, Philadelphia, PA, United StatesDepartment of Otorhinolaryngology−Head and Neck Surgery, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Anesthesiology and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesTraumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury. Although not all pathological structures were stained by all markers at all time points, we found damaged neurons and deformed dendrites in gray matter, punctate and perivascular structures in white matter, and axonal blebs and Wallerian degeneration in both gray and white matter. The present study demonstrates the temporal and structural sensitivities of the three biomarkers: each marker is highly effective for a set of pathological structures, each of which in turn emerges at a particular time point. Furthermore, the different biomarkers showed different abilities at detecting identical types of pathological structures. In contrast to previous studies that have used a single biomarker at a single time range, the present report strongly recommends that a combination of different biomarkers should be adopted and different time points need to be checked when assessing neuropathology after TBI.https://www.frontiersin.org/articles/10.3389/fnins.2024.1339262/fullbrain traumavaricosityaxonal truncationdendritic arborcell debrisβ-Amyloid
spellingShingle Guoxiang Xiong
Ian Jean
Anthony M. Farrugia
Hannah Metheny
Brian N. Johnson
Noam A. Cohen
Noam A. Cohen
Akiva S. Cohen
Akiva S. Cohen
Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
Frontiers in Neuroscience
brain trauma
varicosity
axonal truncation
dendritic arbor
cell debris
β-Amyloid
title Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
title_full Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
title_fullStr Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
title_full_unstemmed Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
title_short Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
title_sort temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse
topic brain trauma
varicosity
axonal truncation
dendritic arbor
cell debris
β-Amyloid
url https://www.frontiersin.org/articles/10.3389/fnins.2024.1339262/full
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