Autor: |
Shah JS; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Macaitis J; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Lundquist B; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Johnstone B; Theratome Bio, Inc., Indianapolis, IN 46202, USA., Coleman M; Theratome Bio, Inc., Indianapolis, IN 46202, USA., Jefferson MA; Air Force Research Laboratory, 711th Human Performance Wing, Airman Systems Directorate, Bioeffects Division, Veterinary Science Branch, San Antonio, TX 78234, USA., Glaser J; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Rodriguez AR; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Cardin S; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Wang HC; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA., Burdette A; Naval Medical Research Unit San Antonio, Fort Sam Houston, San Antonio, TX 78234, USA. |
Abstrakt: |
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. |