Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets
Tóm tắt
The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression. To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical slices. Chemokine and PTGS2 mRNAs remained elevated in slices at 24 h, whereas IL-1β and TNF-α expressions decreased from earlier peak levels. At 24 h after cortical injury in 1-month-old piglets, the expression of CCL2 mRNA was significantly increased in the lesion core and in the penumbra region. The expression of PTGS2, IL-1β, and TNF-α was variable among the piglets. These in vitro and large animal models of cortical injury expand our understanding of the early timing and spread of the immunological response and can serve as preclinical systems to facilitate the discovery of therapeutic agents for TBI aimed at regulating inflammatory mediator expression.
Tài liệu tham khảo
Li LM, Menon DK, Janowitz T. Cross-sectional analysis of data from the US clinical trials database reveals poor translational clinical trial effort for traumatic brain injury compared with stroke. PLoS One. 2014;9:e84336.
Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics. 2010;7:366–77.
Schmidt OI, Heyde CE, Ertel W, Stahel PF. Closed head injury–an inflammatory disease? Brain Res Rev. 2005;48:388–99.
Lu K, Wang Y, Wo YP, Yang Y. Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury. Neurosci Lett. 2005;386:40–5.
Shohami E, Gallily R, Mechoulam R, Bass R, Ben-Hur T. Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J Neuroimmunol. 1997;72:169–77.
Khuman J, Meehan WP, Zhu X, Qiu J, Hoffmann U, Zhang J, et al. Tumor necrosis factor alpha and Fas receptor contribute to cognitive deficits independent of cell death after concussive traumatic brain injury in mice. J Cereb Blood Flow Metab. 2010;31:778–89.
Israelsson C, Bengtsson H, Kylberg A, Kullander K, Lewén A, Hillered L, et al. Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma. 2008;25:959–74.
Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice. J Cereb Blood Flow Metab. 2009;30:769–82.
Kunz T, Marklund N, Hillered L, Oliw EH. Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat. J Neurotrauma. 2002;19:1051–64.
Yang J, You Z, Kim H, Hwang S, Khuman J, Guo S, et al. Genetic analysis of the role of tumor necrosis factor receptors in functional outcome after traumatic brain injury in mice. J Neurotrauma. 2010;27:1037–46.
Frugier T, Morganti-Kossmann MC, O’Reilly D, McLean CA. In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J Neurotrauma. 2010;27:497–507.
Helmy A, Carpenter KL, Menon DK, Pickard JD, Hutchinson PJ. The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab. 2010;31:658–70.
Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev. 2005;1:CD000196.
Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, Hutchinson PJ. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial. J Cereb Blood Flow Metab. 2014;34:845–51.
Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979;311:79–83.
Graber DJ, Harris BT, Hickey WF. Strain-dependent variation in the early transcriptional response to CNS injury using a cortical explant system. J Neuroinflammation. 2011;8:122.
Dzhala V, Valeeva G, Glykys J, Khazipov R, Staley K. Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain. J Neurosci. 2012;32:4017–31.
Duhaime AC, Margulies SS, Durham SR, O’Rourke MM, Golden JA, Marwaha S, et al. Maturation-dependent response of the piglet brain to scaled cortical impact. J Neurosurg. 2000;93:455–62.
Missios S, Harris BT, Dodge CP, Simoni MK, Costine BA, Lee YL, et al. Scaled cortical impact in immature swine: effect of age and gender on lesion volume. J Neurotrauma. 2009;26:1943–51.
Costine B, Quebeda-Clerkin P, Dodge CP, Harris BT, Hillier SC, Duhaime AC. Neuronal-specific enolase, but not S100B nor myelin basic protein, increases in peripheral blood corresponding to lesion volume after cortical impact in piglets. J Neurotrauma. 2012;29:2689–95.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.
Nygard AB, Jorgensen CB, Cirera S, Fredholm M. Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR. BMC Mol Biol. 2007;8:67.
Margulies S, Hicks R. Combination therapies for traumatic brain injury: prospective considerations. J Neurotrauma. 2009;26:925–39.
Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature. 2010;468:253–62.
Pan JZ, Ni L, Sodhi A, Aguanno A, Young W, Hart RP. Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. J Neurosci Res. 2002;68:315–22.
Rice T, Larsen J, Rivest S, Yong VW. Characterization of the early neuroinflammation after spinal cord injury in mice. J Neuropathol Exp Neurol. 2007;66:184–95.
Graber DJ, Hickey WF, Stommel EW, Harris BT. Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury. J Neuroimmune Pharmacol. 2012;7:266–78.
Griesemer A, Yamada K, Sykes M. Xenotransplantation: immunological hurdles and progress toward tolerance. Immunol Rev. 2014;258:241–58.
Costine B, Missios S, Taylor SR, McGuone D, Dodge CP, Harris BD, et al. The subventricular zone in the immature piglet brain: anatomy and exodus of neuroblasts into white matter after traumatic brain injury. Dev Neurosci. 2015;37. Epub ahead of print.
Bauman RA, Ling G, Tong L, Januszkiewicz A, Agoston D, Delanerolle N, et al. An introductory characterization of a combat-casualty-care relevant swine model of closed head injury resulting from exposure to explosive blast. J Neurotrauma. 2009;26:841–60.