Cargando…
Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast
A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the im...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275793/ https://www.ncbi.nlm.nih.gov/pubmed/22403567 http://dx.doi.org/10.3389/fneur.2012.00015 |
_version_ | 1782223271223099392 |
---|---|
author | Svetlov, Stanislav I. Prima, Victor Glushakova, Olena Svetlov, Artem Kirk, Daniel R. Gutierrez, Hector Serebruany, Victor L. Curley, Kenneth C. Wang, Kevin K. W. Hayes, Ronald L. |
author_facet | Svetlov, Stanislav I. Prima, Victor Glushakova, Olena Svetlov, Artem Kirk, Daniel R. Gutierrez, Hector Serebruany, Victor L. Curley, Kenneth C. Wang, Kevin K. W. Hayes, Ronald L. |
author_sort | Svetlov, Stanislav I. |
collection | PubMed |
description | A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. In this study, we further characterized blast producing moderate traumatic brain injury and defined “composite” blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast), but negligible skull movement upon peak overpressure exposure off-axis (primary blast). Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, soluble intercellular adhesion molecule-1, and L-selectin along with neurotrophic factor nerve growth factor-beta were increased in serum within 6 h post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with unprotected body. |
format | Online Article Text |
id | pubmed-3275793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-32757932012-03-08 Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast Svetlov, Stanislav I. Prima, Victor Glushakova, Olena Svetlov, Artem Kirk, Daniel R. Gutierrez, Hector Serebruany, Victor L. Curley, Kenneth C. Wang, Kevin K. W. Hayes, Ronald L. Front Neurol Neurology A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. In this study, we further characterized blast producing moderate traumatic brain injury and defined “composite” blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast), but negligible skull movement upon peak overpressure exposure off-axis (primary blast). Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, soluble intercellular adhesion molecule-1, and L-selectin along with neurotrophic factor nerve growth factor-beta were increased in serum within 6 h post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release, particularly when primary blast impacted rats with unprotected body. Frontiers Research Foundation 2012-02-09 /pmc/articles/PMC3275793/ /pubmed/22403567 http://dx.doi.org/10.3389/fneur.2012.00015 Text en Copyright © 2012 Svetlov, Prima, Glushakova, Svetlov, Kirk, Gutierrez, Serebruany, Curley, Wang and Hayes. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Neurology Svetlov, Stanislav I. Prima, Victor Glushakova, Olena Svetlov, Artem Kirk, Daniel R. Gutierrez, Hector Serebruany, Victor L. Curley, Kenneth C. Wang, Kevin K. W. Hayes, Ronald L. Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title | Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title_full | Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title_fullStr | Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title_full_unstemmed | Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title_short | Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast |
title_sort | neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to “composite” blast |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275793/ https://www.ncbi.nlm.nih.gov/pubmed/22403567 http://dx.doi.org/10.3389/fneur.2012.00015 |
work_keys_str_mv | AT svetlovstanislavi neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT primavictor neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT glushakovaolena neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT svetlovartem neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT kirkdanielr neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT gutierrezhector neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT serebruanyvictorl neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT curleykennethc neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT wangkevinkw neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast AT hayesronaldl neuroglialandsystemicmechanismsofpathologicalresponsesinratmodelsofprimaryblastoverpressurecomparedtocompositeblast |