Cargando…

Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma

Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-...

Descripción completa

Detalles Bibliográficos
Autores principales: Shah, Jessica Stukel, Macaitis, Joseph, Lundquist, Bridney, Johnstone, Brian, Coleman, Michael, Jefferson, Michelle A., Glaser, Jacob, Rodriguez, Annette R., Cardin, Sylvain, Wang, Heuy-Ching, Burdette, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604349/
https://www.ncbi.nlm.nih.gov/pubmed/36293520
http://dx.doi.org/10.3390/ijms232012664
_version_ 1784817791537250304
author Shah, Jessica Stukel
Macaitis, Joseph
Lundquist, Bridney
Johnstone, Brian
Coleman, Michael
Jefferson, Michelle A.
Glaser, Jacob
Rodriguez, Annette R.
Cardin, Sylvain
Wang, Heuy-Ching
Burdette, Alexander
author_facet Shah, Jessica Stukel
Macaitis, Joseph
Lundquist, Bridney
Johnstone, Brian
Coleman, Michael
Jefferson, Michelle A.
Glaser, Jacob
Rodriguez, Annette R.
Cardin, Sylvain
Wang, Heuy-Ching
Burdette, Alexander
author_sort Shah, Jessica Stukel
collection PubMed
description Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic.
format Online
Article
Text
id pubmed-9604349
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96043492022-10-27 Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma Shah, Jessica Stukel Macaitis, Joseph Lundquist, Bridney Johnstone, Brian Coleman, Michael Jefferson, Michelle A. Glaser, Jacob Rodriguez, Annette R. Cardin, Sylvain Wang, Heuy-Ching Burdette, Alexander Int J Mol Sci Article Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic. MDPI 2022-10-21 /pmc/articles/PMC9604349/ /pubmed/36293520 http://dx.doi.org/10.3390/ijms232012664 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shah, Jessica Stukel
Macaitis, Joseph
Lundquist, Bridney
Johnstone, Brian
Coleman, Michael
Jefferson, Michelle A.
Glaser, Jacob
Rodriguez, Annette R.
Cardin, Sylvain
Wang, Heuy-Ching
Burdette, Alexander
Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title_full Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title_fullStr Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title_full_unstemmed Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title_short Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma
title_sort evaluating thera-101 as a low-volume resuscitation fluid in a model of polytrauma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604349/
https://www.ncbi.nlm.nih.gov/pubmed/36293520
http://dx.doi.org/10.3390/ijms232012664
work_keys_str_mv AT shahjessicastukel evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT macaitisjoseph evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT lundquistbridney evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT johnstonebrian evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT colemanmichael evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT jeffersonmichellea evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT glaserjacob evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT rodriguezannetter evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT cardinsylvain evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT wangheuyching evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma
AT burdettealexander evaluatingthera101asalowvolumeresuscitationfluidinamodelofpolytrauma