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Brain proteomic changes by histone deacetylase inhibition after traumatic brain injury
- Source :
- Trauma Surgery & Acute Care Open, Trauma Surgery & Acute Care Open, Vol 6, Iss 1 (2021)
- Publication Year :
- 2021
-
Abstract
- BackgroundTraumatic brain injury (TBI) is a leading cause of morbidity and mortality. There are currently no cytoprotective treatments for TBI. There is growing evidence that the histone deacetylase inhibitor valproic acid (VPA) may be beneficial in the treatment of TBI associated with hemorrhagic shock and in isolation. We sought to further evaluate the mechanistic underpinnings of this demonstrated efficacy via proteomic analysis of injured brain tissue.MethodsSwine were subjected to TBI via controlled cortical impact, randomized to treatment with VPA or control and observed for 6 hours. The brains of the pigs were then sectioned, and tissue was prepared and analyzed for proteomic data, including gene ontology (GO), gene-set enrichment analysis and enrichment mapping, and network mapping.ResultsProteomic analysis demonstrated differential expression of hundreds of proteins in injured brain tissue after treatment with VPA. GO analysis and network analyses revealed groups of proteins and processes that are known to modulate injury response after TBI and impact cell fate. Processes affected included protein targeting and transport, cation and G-protein signaling, metabolic response, neurotransmitter response and immune function.DiscussionThis proteomic analysis provides initial mechanistic insight into the observed rescue of injured brain tissue after VPA administration in isolated TBI.Level of evidenceNot applicable (animal study).
- Subjects :
- RD1-811
Traumatic brain injury
medicine.drug_class
Cell fate determination
Pharmacology
histone deacetylase inhibitors
Critical Care and Intensive Care Medicine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
cytoprotection
valproic acid
TBI
medicine
Neurotransmitter
Original Research
Valproic Acid
business.industry
RC86-88.9
Histone deacetylase inhibitor
030208 emergency & critical care medicine
Medical emergencies. Critical care. Intensive care. First aid
medicine.disease
Cytoprotection
chemistry
Surgery
Histone deacetylase
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 23975776
- Volume :
- 6
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Trauma surgeryacute care open
- Accession number :
- edsair.doi.dedup.....d0db4b723ae6b1f920660a9805a5b6ca