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Early single-dose exosome treatment improves neurologic outcomes in a 7-day swine model of traumatic brain injury and hemorrhagic shock
- Source :
- Journal of Trauma and Acute Care Surgery. 89:388-396
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- BACKGROUND Early single-dose treatment with human mesenchymal stem cell-derived exosomes promotes neuroprotection and promotes blood-brain barrier integrity in models of traumatic brain injury (TBI) and hemorrhagic shock (HS) in swine. The impact of an early single dose of exosomes on late survival (7 days), however, remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on neurologic outcomes, brain lesion size, inflammatory cytokines, apoptotic markers, and mediators of neural plasticity in a 7-day survival model. METHODS Yorkshire swine were subjected to a severe TBI (8-mm cortical impact) and HS (40% estimated total blood volume). After 1 hour of shock, animals were randomized (n = 4/cohort) to receive either lactated Ringer's (5 mL) or lactated Ringer's with exosomes (1 × 10 exosome particles). After an additional hour of shock, animals were resuscitated with normal saline. Daily neurologic severity scores were compared. At 7 days following injury, lesion size, inflammatory markers, and mediators of inflammation (NF-κB), apoptosis (BAX), and neural plasticity (brain-derived neurotrophic factor) in brain tissue were compared between groups. RESULTS Exosome-treated animals had significantly lower neurologic severity scores (first 4 days; p < 0.05) and faster neurologic recovery. At 7 days, exosome-treated animals had significantly smaller (p < 0.05) brain lesion sizes. Exosome-treated animals also had significantly lower levels of inflammatory markers (interleukin [IL]-1, IL-6, IL-8, and IL-18) and higher granulocyte-macrophage colony-stimulating factor levels compared with the control animals, indicating specific impacts on various cytokines. The BAX and NF-κB levels were significantly lower (p < 0.05) in exosome-treated animals, while brain-derived neurotrophic factor levels were significantly higher (p < 0.05) in the exosome-treated animals. CONCLUSION In a large animal model of TBI and HS, early single-dose exosome treatment attenuates neurologic injury, decreases brain lesion size, inhibits inflammation and apoptosis, and promotes neural plasticity over a 7-day period.
- Subjects :
- medicine.medical_specialty
Swine
Traumatic brain injury
Apoptosis
Inflammation
Shock, Hemorrhagic
Exosomes
Critical Care and Intensive Care Medicine
Exosome
Neuroprotection
Proinflammatory cytokine
Lesion
03 medical and health sciences
0302 clinical medicine
Neurotrophic factors
Internal medicine
Brain Injuries, Traumatic
medicine
Animals
bcl-2-Associated X Protein
business.industry
Hemodynamics
NF-kappa B
Mesenchymal Stem Cells
030208 emergency & critical care medicine
medicine.disease
Disease Models, Animal
Treatment Outcome
Endocrinology
Blood-Brain Barrier
Shock (circulatory)
Cytokines
Female
Surgery
medicine.symptom
business
Signal Transduction
Subjects
Details
- ISSN :
- 21630763 and 21630755
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Journal of Trauma and Acute Care Surgery
- Accession number :
- edsair.doi.dedup.....54a8de43495558508b534c8b3fe936b8