Modulation of Brain Transcriptome by Combined Histone Deacetylase Inhibition and Plasma Treatment Following Traumatic Brain Injury and Hemorrhagic Shock.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
pubmed:
15
9
2020
medline:
16
12
2021
entrez:
14
9
2020
Statut:
ppublish
Résumé
We previously showed that the addition of valproic acid (VPA), a histone deacetylase inhibitor, to fresh frozen plasma (FFP) resuscitation attenuates brain lesion size and swelling following traumatic brain injury (TBI) and hemorrhagic shock (HS). The goal of this study was to use computational biology tools to investigate the effects of FFP+VPA on the brain transcriptome following TBI+HS. Swine underwent TBI+HS, kept in shock for 2 h, and resuscitated with FFP or FFP + VPA (n = 5/group). After 6 h of observation, brain RNA was isolated and gene expression was analyzed using a microarray. iPathwayGuide, Gene Ontology (GO), Gene-Set Enrichment Analysis, and Enrichment Mapping were used to identify significantly impacted genes and transcriptomic networks. Eight hundred differentially expressed (DE) genes were identified out of a total of 9,118 genes. Upregulated genes were involved in promotion of cell division, proliferation, and survival, while downregulated genes were involved in autophagy, cell motility, neurodegenerative diseases, tumor suppression, and cell cycle arrest. Seven hundred ninety-one GO terms were significantly enriched. A few major transcription factors, such as TP53, NFKB3, and NEUROD1, were responsible for modulating hundreds of other DE genes. Network analysis revealed attenuation of interconnected genes involved in inflammation and tumor suppression, and an upregulation of those involved in cell proliferation and differentiation. Overall, these results suggest that VPA treatment creates an environment that favors production of new neurons, removal of damaged cells, and attenuation of inflammation, which could explain its previously observed neuroprotective effects.
Identifiants
pubmed: 32925172
pii: 00024382-202101000-00015
doi: 10.1097/SHK.0000000000001605
doi:
Substances chimiques
Enzyme Inhibitors
0
Histone Deacetylase Inhibitors
0
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110-120Informations de copyright
Copyright © 2020 by the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Centers for Disease Control and Prevention. TBI data and statistics. Atlanta, Georgia, United States. 2014. Available at: http://www.cdc.gov/traumaticbraininjury/data/ . Accessed April 18, 2019.
McMahon CG, Yates DW, Campbell FM, Hollis S, Woodford M. Unexpected contribution of moderate traumatic brain injury to death after major trauma. J Trauma 47:891–895, 1999.
Desai KH, Tan CS, Leek JT, Maier RV, Tompkins RG, Storey JD. Inflammation and the Host Response to Injury Large-Scale Collaborative Research Program. Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a longitudinal clinical genomics study. PLoS Med 8 (9):e1001093, 2011.
Santry HP, Alam HB. Fluid resuscitation: past, present, and the future. Shock 33 (3):229–241, 2010.
Dekker SE, Sillesen M, Bambakidis T, Jin G, Liu B, Boer C, Johansson PI, Halaweish I, Maxwell J, Alam HB. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs. Surgery 156 (3):556–563, 2014.
Butler FK, Holcomb JB, Schreiber MA, Kotwal RS, Jenkins DA, Champion HR, Bowling F, Cap AP, Dubose JJ, Dorlac WC, et al. Fluid resuscitation for hemorrhagic shock in tactical combat casualty care: TCCC Guidelines Change 14-01—2 June 2014. J Spec Oper Med 14 (3):13–23, 2014.
Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 313 (5):471–482, 2015.
Halaweish I, Bambakidis T, He W, Linzel D, Chang Z, Srinivasan A, Dekker SE, Liu B, Li Y, Alam HB. Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. J Am Coll Surg 220 (5):809–819, 2015.
Jin G, Duggan M, Imam A, Demoya MA, Sillesen M, Hwabejire J, Jepsen CH, Liu B, Mejaddam AY, Lu J, et al. Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury. J Trauma Acute Care Surg 73 (6):1461–1470, 2012.
Halaweish I, Bambakidis T, Chang Z, Wei H, Liu B, Li Y, Bonthrone T, Srinivasan A, Bonham T, Chtraklin K, et al. Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock. J Trauma Acute Care Surg 79 (6):911–919, 2015.
Sillesen M, Bambakidis T, Dekker SE, Li Y, Alam HB. Fresh frozen plasma modulates brain gene expression in a swine model of traumatic brain injury and shock: a network analysis. J Am Coll Surg 224 (1):49–58, 2017.
Imam AM, Jin G, Duggan M, Sillesen M, Hwabejire JO, Jepsen CH, DePeralta D, Liu B, Lu J, deMoya MA, et al. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock. Surgery 154 (2):388–396, 2013.
Prevost TP, Jin G, de Moya MA, Alam HB, Suresh S, Socrate S. Dynamic mechanical response of brain tissue in indentation in vivo, in situ and in vitro. Acta Biomater 7 (12):4090–4101, 2011.
Jin G, DeMoya MA, Duggan M, Knightly T, Mejaddam AY, Hwabejire J, Lu J, Smith WM, Kasotakis G, Velmahos GC, et al. Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults. Shock 38 (1):49–56, 2012.
Dekker SE, Bambakidis T, Sillesen M, Liu B, Johnson CN, Jin G, Li Y, Alam HB. Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage. J Trauma Acute Care Surg 77 (6):906–912, 2014.
Bambakidis T, Dekker SE, Sillesen M, Liu B, Johnson CN, Jin G, de Vries HE, Li Y, Alam HB. Resuscitation with valproic acid alters inflammatory genes in a porcine model of combined traumatic brain injury and hemorrhagic shock. J Neurotrauma 33 (16):1514–1521, 2016.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B (Methodol) 57 (1):289–300, 1995.
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25 (1):25–29, 2000.
Alexa A, Rahnenführer J, Lengauer T. Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 22 (13):1600–1607, 2006.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102 (43):15545–15550, 2005.
Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 5 (11):e13984, 2010.
Higgins GA, Georgoff P, Nikolian V, Allyn-Feuer A, Pauls B, Higgins R, Athey BD, Alam HE. Network reconstruction reveals that valproic acid activates neurogenic transcriptional programs in adult brain following traumatic injury. Pharm Res 34 (8):1658–1672, 2017.
Nikolian VC, Dennahy IS, Higgins GA, Williams AM, Weykamp M, Georgoff PE, Eidy H, Ghandour MH, Chang P, Alam HB. Transcriptomic changes following valproic acid treatment promote neurogenesis and minimize secondary brain injury. J Trauma Acute Care Surg 84 (3):459–465, 2018.
Guyette FX, Sperry JL, Peitzman AB, Billiar TR, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Putnam T, Duane TM, et al. Prehospital blood product and crystalloid resuscitation in the severely injured patient: a secondary analysis of the prehospital air medical plasma trial. Ann Surg 2019; Online ahead of print.
Georgoff PE, Nikolian VC, Halaweish I, Chtraklin K, Bruhn PJ, Eidy H, Rasmussen M, Li Y, Srinivasan A, Alam HB. Resuscitation with lyophilized plasma is safe and improves neurological recovery in a long-term survival model of swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma. J Neurotrauma 34 (13):2167–2175, 2017.
Williams AM, Bhatti UF, Biesterveld BE, Graham NJ, Chtraklin K, Zhou J, Dennahy IS, Kathawate RG, Vercruysse CA, Russo RM, et al. Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation. J Trauma Acute Care Surg 87 (2):393–401, 2019.
Nikolian VC, Georgoff PE, Pai MP, Dennahy IS, Chtraklin K, Eidy H, Ghandour MH, Han Y, Srinivasan A, Li Y, et al. Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma. J Trauma Acute Care Surg 83 (6):1066–1073, 2017.
Chang P, Williams AM, Bhatti UF, Biesterveld BE, Liu B, Nikolian VC, Dennahy IS, Lee J, Li Y, Alam HB. Valproic acid and neural apoptosis, inflammation, and degeneration 30 days after traumatic brain injury, hemorrhagic shock, and polytrauma in a swine model. J Am Coll Surg 228 (3):265–275, 2019.
Georgoff PE, Nikolian VC, Higgins G, Chtraklin K, Eidy H, Ghandour MH, Williams A, Athey B, Alam HB. Valproic acid induces prosurvival transcriptomic changes in swine subjected to traumatic injury and hemorrhagic shock. J Trauma Acute Care Surg 84 (4):642–649, 2018.
Nikolian VC, Dekker SE, Bambakidis T, Higgins GA, Dennahy IS, Georgoff PE, Williams AM, Andjelkovic AV, Alam HB. Improvement of blood-brain barrier integrity in traumatic brain injury and hemorrhagic shock following treatment with valproic acid and fresh frozen plasma. Crit Care Med 46 (1):e59–e66, 2018.
Williams AM, Dennahy IS, Bhatti UF, Biesterveld BE, Graham NJ, Li Y, Alam HB. Histone deacetylase inhibitors: a novel strategy in trauma and sepsis. Shock 52 (3):300–306, 2019.
Dekker SE, Nikolian VC, Sillesen M, Bambakidis T, Schober P, Alam HB. Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury. J Neurosci Res 96 (4):711–719, 2018.
Dekker SE, Sillesen M, Bambakidis T, Andjelkovic AV, Jin G, Liu B, Boer C, Johansson PI, Linzel D, Halaweish I, et al. Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in a large animal model of traumatic brain injury and hemorrhagic shock. J Surg Res 190 (1):312–318, 2014.
Hinson HE, Rowell S, Schreiber M. Clinical evidence of inflammation driving secondary brain injury: a systematic review. J Trauma Acute Care Surg 78 (1):184–191, 2015.
Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, et al. The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172 (10):6362–6372, 2015.
Luo Q, Lin H, Ye X, Huang J, Lu S, Xu L. Trim44 facilitates the migration and invasion of human lung cancer cells via the NF-κB signaling pathway. Int J Clin Oncol 20 (3):508–517, 2015.
Li R, Aslan A, Yan R, Jongman RM, Moser J, Zwiers PJ, Moorlag HE, Zijlstra JG, Molema G, van Meurs M. Histone deacetylase inhibition and I(B kinase/nuclear factor-κB blockade ameliorate microvascular proinflammatory responses associated with hemorrhagic shock/resuscitation in mice. Crit Care Med 43 (12):e567–e580, 2015.
Hu Q, Khanna P, Ee Wong BS, Lin Heng ZS, Subhramanyam CS, Thanga LZ, Sing Tan SW, Baeg GH. Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation. Oncotarget 9 (3):4223–4238, 2017.
Aubrey BJ, Strasser A, Kelly GL. Tumor-suppressor functions of the TP53 pathway. Cold Spring Harb Perspect Med 6 (5):a026062, 2016.
Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell 137 (3):413–431, 2009.
Brochier C, Dennis G, Rivieccio MA, McLaughlin K, Coppola G, Ratan RR, Langley B. Specific acetylation of p53 by HDAC inhibition prevents DNA damage-induced apoptosis in neurons. J Neurosci 33 (20):8621–8632, 2013.
Muñoz-Pinedo C. Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense. Adv Exp Med Biol 738:124–143, 2012.
Janikiewicz J, Szymański J, Malinska D, Patalas-Krawczyk P, Michalska B, Duszyński J, Giorgi C, Bonora M, Dobrzyn A, Wieckowski MR. Mitochondria-associated membranes in aging and senescence: structure, function, and dynamics. Cell Death Dis 9 (3):332, 2018.
Alessandri B, Heimann A, Filippi R, Kopacz L, Kempski O. Moderate controlled cortical contusion in pigs: effects on multi-parametric neuromonitoring and clinical relevance. J Neurotrauma 20 (12):1293–1305, 2003.
Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci 14 (2):128–214, 2013.