Development of a systems-based in situ multiplex biomarker screening approach for the assessment of immunopathology and neural tissue plasticity in male rats after traumatic brain injury - PubMed (original) (raw)
. 2018 Apr;96(4):487-500.
doi: 10.1002/jnr.24054. Epub 2017 May 2.
Affiliations
- PMID: 28463430
- PMCID: PMC5668208
- DOI: 10.1002/jnr.24054
Development of a systems-based in situ multiplex biomarker screening approach for the assessment of immunopathology and neural tissue plasticity in male rats after traumatic brain injury
Tanya Bogoslovsky et al. J Neurosci Res. 2018 Apr.
Abstract
Traumatic brain injuries (TBIs) pose a massive burden of disease and continue to be a leading cause of morbidity and mortality throughout the world. A major obstacle in developing effective treatments is the lack of comprehensive understanding of the underlying mechanisms that mediate tissue damage and recovery after TBI. As such, our work aims to highlight the development of a novel experimental platform capable of fully characterizing the underlying pathobiology that unfolds after TBI. This platform encompasses an empirically optimized multiplex immunohistochemistry staining and imaging system customized to screen for a myriad of biomarkers required to comprehensively evaluate the extent of neuroinflammation, neural tissue damage, and repair in response to TBI. Herein, we demonstrate that our multiplex biomarker screening platform is capable of evaluating changes in both the topographical location and functional states of resident and infiltrating cell types that play a role in neuropathology after controlled cortical impact injury to the brain in male Sprague-Dawley rats. Our results demonstrate that our multiplex biomarker screening platform lays the groundwork for the comprehensive characterization of changes that occur within the brain after TBI. Such work may ultimately lead to the understanding of the governing pathobiology of TBI, thereby fostering the development of novel therapeutic interventions tailored to produce optimal tissue protection, repair, and/or regeneration with minimal side effects, and may ultimately find utility in a wide variety of other neurological injuries, diseases, and disorders that share components of TBI pathobiology.
Keywords: controlled cortical impact (CCI); immunopathology; multiplex immunohistology; neural plasticity; systems biology; traumatic brain injury (TBI).
Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Conflict of interest statement
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Figures
Figure 1
(a) Evaluation of tissue damage 24 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (b) Bright field phase contrast images of enclosed areas in 1a comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3) on the ipsilateral side, with A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. (c) Evaluation of tissue damage 72 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (d) Bright field phase contrast images of enclosed areas in 1c comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3). A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. A and B regions are comparable to those at 24 h post-CCI.
Figure 1
(a) Evaluation of tissue damage 24 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (b) Bright field phase contrast images of enclosed areas in 1a comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3) on the ipsilateral side, with A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. (c) Evaluation of tissue damage 72 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (d) Bright field phase contrast images of enclosed areas in 1c comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3). A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. A and B regions are comparable to those at 24 h post-CCI.
Figure 1
(a) Evaluation of tissue damage 24 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (b) Bright field phase contrast images of enclosed areas in 1a comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3) on the ipsilateral side, with A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. (c) Evaluation of tissue damage 72 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (d) Bright field phase contrast images of enclosed areas in 1c comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3). A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. A and B regions are comparable to those at 24 h post-CCI.
Figure 1
(a) Evaluation of tissue damage 24 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (b) Bright field phase contrast images of enclosed areas in 1a comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3) on the ipsilateral side, with A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. (c) Evaluation of tissue damage 72 h post-CCI (left parietooccipital area) via H+E staining (coronal section at level of impact). (d) Bright field phase contrast images of enclosed areas in 1c comparing morphological changes in the cerebral cortex/matched areas within the ipsilateral and contralateral hemispheres, including the zoomed in areas showing the subarachnoid hematoma at the impact site (B1), as well as hematoma in the external pyramidal layer (B2) and white matter in corpus callosum (B3). A1, A2, and A3 matching areas within the contralateral hemispheres serving as internal controls. A and B regions are comparable to those at 24 h post-CCI.
Figure 2
Changes in the neuronal cytoarchitecture adjacent to the site of cortical impact at 24 h post-CCI; NeuN (green), CD57 (red), parvalbumin (purple), GAD67 (cyan)
Figure 3
Changes in oligodendrocyte cytoarchitecture adjacent to the site of cortical impact at 24 h post-CCI; APC (red), MBP (blue)
Figure 4
Changes in astrocyte cytoarchitecture adjacent to the site of cortical impact at 24 h post-CCI; nestin (yellow), GFAP (orange).
Figure 5
Changes in microglial and endothelial morphology and activation in areas adjacent to the site of cortical impact at 24 h post-CCI; IB4 (aquamarine), Iba1 (magenta)
Figure 6
Merged composite of 10 relevant biomarkers shown in Figures 2–5 revealing changes to cortical cytoarchitecture 24 h post-CCI.
Figure 7
Changes in the neuronal cytoarchitecture adjacent to the site of cortical impact at 72 h post-CCI; NeuN (green), CD57 (red), parvalbumin (purple), GAD67 (cyan)
Figure 8
Changes in oligodendrocyte cytoarchitecture adjacent to the site of cortical impact at 72 h post-CCI; APC (red), MBP (blue)
Figure 9
Changes in astrocyte cytoarchitecture adjacent to the site of cortical impact at 72 h post-CCI; nestin (yellow), GFAP (orange).
Figure 10
Changes in microglial and endothelial morphology and activation in areas adjacent to the site of cortical impact at 72 h post-CCI; IB4 (aquamarine), Iba1 (magenta)
Figure 11
Merged composite of 10 relevant biomarkers shown in Figures 7–10 revealing changes to cortical cytoarchitecture 72 h post-CCI.
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