Interference with protease-activated receptor 1 does not reduce damage to subventricular zone cells of immature rodent brain following exposure to blood or blood plasma

Journal of Negative Results in Biomedicine

Marc R Del Bigio¹  Xiaoyan Mao¹ 

[1] Department of Pathology, University of Manitoba, and Children’s Hospital Research Institute of Manitoba, 401 Brodie Centre, 715 McDermot Avenue, Winnipeg R3E 3P5, MB, Canada

关键词: Cell proliferation;    Coagulation factor II receptor;    Thrombin receptor;    Subventricular zone;    Brain hemorrhage;    Prematurity;   

Others  :  1133134
DOI  :  10.1186/s12952-014-0022-4

 received in 2014-07-17, accepted in 2014-12-22,  发布年份 2015

【 摘 要 】

Background

Prior work showed that whole blood, plasma, and serum injections are damaging to the neonatal rodent brain in a model of intracerebral/periventricular hemorrhage. Thrombin alone is also damaging. In adult animal models of hemorrhagic stroke, the protease-activated (thrombin) receptor PAR1 mediates some of the brain damage. We hypothesized that PAR1 interference will reduce the adverse effects of blood products on immature rodent brain and cells.

Results

Cultured oligodendrocyte precursor cells from rats and mice were exposed to blood plasma with and without the PAR1 antagonists SCH-79797 or BMS-200261. In concentrations previously shown to have activity on brain cells, neither drug showed evidence of protection against the toxicity of blood plasma. Newborn mice (wild type, heterozygous, and PAR1 knockout) were subjected to intracerebral injection of autologous whole blood into the periventricular region of the frontal lobe. Cell proliferation, measured by Ki67 immunoreactivity in the subventricular zone, was suppressed at 1 and 2 days, and was not normalized in the knockout mice. Cell apoptosis, measured by activated caspase 3 immunoreactivity, was not apparent in the subventricular zone. Increased apoptosis in periventricular striatal cells was not normalized in the knockout mice.

Conclusion

Interference with the thrombin-PAR1 system does not reduce the adverse effects of blood on germinal cells of the immature rodent brain. PAR1 interference is unlikely to be a useful treatment for reducing the brain damage that accompanies periventricular (germinal matrix) hemorrhage, a common complication of premature birth.

【 授权许可】

   
2015 Mao and Del Bigio; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Del Bigio MR: Hemorrhagic Lesions. In Developmental Neuropathology. Edited by Golden JA, Harding BN. International Society of Neuropathology Press, Basel, Switzerland; 2004:150-5.
• [2]Del Bigio MR: Cell proliferation in human ganglionic eminence and suppression after prematurity-associated haemorrhage. Brain 2011, 134:1344-61.
• [3]Xue M, Balasubramaniam J, Buist RJ, Peeling J, Del Bigio MR: Periventricular/intraventricular hemorrhage in neonatal mouse cerebrum. J Neuropathol Exp Neurol 2003, 62:1154-65.
• [4]Ballabh P: Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res 2010, 67:1-8.
• [5]Xue M, Del Bigio MR: Injections of blood, thrombin, and plasminogen more severely damage neonatal mouse brain than mature mouse brain. Brain Pathol 2005, 15:273-80.
• [6]Xue M, Balasubramaniam J, Parsons KA, McIntyre IW, Peeling J, Del Bigio MR: Does thrombin play a role in the pathogenesis of brain damage after periventricular hemorrhage? Brain Pathol 2005, 15:241-9.
• [7]Juliet PA, Frost EE, Balasubramaniam J, Del Bigio MR: Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture. J Neurochem 2009, 109:1285-99.
• [8]Siller-Matula JM, Schwameis M, Blann A, Mannhalter C, Jilma B: Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects. Thromb Haemost 2011, 106:1020-33.
• [9]Babu R, Bagley JH, Di C, Friedman AH, Adamson C: Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention. Neurosurg Focus 2012, 32:E8.
• [10]Cheng Y, Xi G, Jin H, Keep RF, Feng J, Hua Y: Thrombin-induced cerebral hemorrhage: role of proteaseactivated receptor-1. Transl Stroke Res 2014, 5:472-475.
• [11]Coughlin SR: Thrombin signalling and protease-activated receptors. Nature 2000, 407:258-64.
• [12]Mannaioni G, Orr AG, Hamill CE, Yuan H, Pedone KH, McCoy KL, et al.: Plasmin potentiates synaptic N-methyl-D-aspartate receptor function in hippocampal neurons through activation of protease-activated receptor-1. J Biol Chem 2008, 283:20600-11.
• [13]Burda JE, Radulovic M, Yoon H, Scarisbrick IA: Critical role for PAR1 in kallikrein 6-mediated oligodendrogliopathy. Glia 2013, 61:1456-70.
• [14]Wang Y, Richter-Landsberg C, Reiser G: Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial cells and mechanism of PAR-1-induced calcium signaling. Neuroscience 2004, 126:69-82.
• [15]Grade S, Agasse F, Bernardino L, Silva CG, Cortes L, Malva JO: Functional identification of neural stem cell-derived oligodendrocytes by means of calcium transients elicited by thrombin. Rejuvenation Res 2010, 13:27-37.
• [16]Wang Y, Luo W, Wartmann T, Halangk W, Sahin-Toth M, Reiser G: Mesotrypsin, a brain trypsin, activates selectively proteinase-activated receptor-1, but not proteinase-activated receptor-2, in rat astrocytes. J Neurochem 2006, 99:759-69.
• [17]Maeda S, Nakajima K, Tohyama Y, Kohsaka S: Characteristic response of astrocytes to plasminogen/plasmin to upregulate transforming growth factor beta 3 (TGFbeta3) production/secretion through proteinase-activated receptor-1 (PAR-1) and the downstream phosphatidylinositol 3-kinase (PI3K)-Akt/PKB signaling cascade. Brain Res 2009, 1305:1-13.
• [18]Thevenet J, Angelillo-Scherrer A, Price M, Hirt L: Coagulation factor Xa activates thrombin in ischemic neural tissue. J Neurochem 2009, 111:828-36.
• [19]Manaenko A, Sun X, Kim CH, Yan J, Ma Q, Zhang JH: PAR-1 antagonist SCH79797 ameliorates apoptosis following surgical brain injury through inhibition of ASK1-JNK in rats. Neurobiol Dis 2013, 50:13-20.
• [20]Junge CE, Sugawara T, Mannaioni G, Alagarsamy S, Conn PJ, Brat DJ, et al.: The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc Natl Acad Sci U S A 2003, 100:13019-24.
• [21]Sturrock RR, Smart IH: A morphological study of the mouse subependymal layer from embryonic life to old age. J Anat 1980, 130:391-415.
• [22]Smart I: The subependymal layer of the mouse brain and its cell production as shown by radioautography after thymidine-H3 injection. J Comp Neurol 1961, 116:325-47.
• [23]Marshall CA, Novitch BG, Goldman JE: Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells. J Neurosci 2005, 25:7289-98.
• [24]Jang ES, Goldman JE: Pax6 expression is sufficient to induce a neurogenic fate in glial progenitors of the neonatal subventricular zone. PLoS One 2011, 6:e20894.
• [25]Tramontin AD, Garcia-Verdugo JM, Lim DA, Alvarez-Buylla A: Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb Cortex 2003, 13:580-7.
• [26]Nicole O, Goldshmidt A, Hamill CE, Sorensen SD, Sastre A, Lyuboslavsky P, et al.: Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J Neurosci 2005, 25:4319-29.
• [27]Suo Z, Wu M, Ameenuddin S, Anderson HE, Zoloty JE, Citron BA, et al.: Participation of protease-activated receptor-1 in thrombin-induced microglial activation. J Neurochem 2002, 80:655-66.
• [28]Di Serio C, Pellerito S, Duarte M, Massi D, Naldini A, Cirino G, et al.: Protease-activated receptor 1-selective antagonist SCH79797 inhibits cell proliferation and induces apoptosis by a protease-activated receptor 1-independent mechanism. Basic Clin Pharmacol Toxicol 2007, 101:63-9.
• [29]Hamill CE, Mannaioni G, Lyuboslavsky P, Sastre AA, Traynelis SF: Protease-activated receptor 1-dependent neuronal damage involves NMDA receptor function. Exp Neurol 2009, 217:136-46.
• [30]Wang J, Jin H, Hua Y, Keep RF, Xi G: Role of protease-activated receptor-1 in brain injury after experimental global cerebral ischemia. Stroke 2012, 43:2476-82.
• [31]Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR: A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 2001, 293:1666-70.
• [32]Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, et al.: Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell 2010, 18:25-38.
• [33]The Gene Expression Nervous System Atlas (GENSAT) Project [http://www.gensat.org/about.jsp]
• [34]Shimogori T, Lee DA, Miranda-Angulo A, Yang Y, Wang H, Jiang L, et al.: A genomic atlas of mouse hypothalamic development. Nat Neurosci 2010, 13:767-75.
• [35]Niclou SP, Suidan HS, Pavlik A, Vejsada R, Monard D: Changes in the expression of protease-activated receptor 1 and protease nexin-1 mRNA during rat nervous system development and after nerve lesion. Eur J Neurosci 1998, 10:1590-607.
• [36]Clancy B, Darlington RB, Finlay BL: Translating developmental time across mammalian species. Neuroscience 2001, 105:7-17.
• [37]Cheung AF, Pollen AA, Tavare A, DeProto J, Molnar Z: Comparative aspects of cortical neurogenesis in vertebrates. J Anat 2007, 211:164-76.
• [38]Dehay C, Kennedy H: Cell-cycle control and cortical development. Nat Rev Neurosci 2007, 8:438-50.
• [39]Yoon H, Radulovic M, Wu J, Blaber SI, Blaber M, Fehlings MG, et al.: Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity. J Neurochem 2013, 127:283-98.
• [40]Guo H, Liu D, Gelbard H, Cheng T, Insalaco R, Fernandez JA, et al.: Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3. Neuron 2004, 41:563-72.
• [41]Suo Z, Wu M, Citron BA, Gao C, Festoff BW: Persistent protease-activated receptor 4 signaling mediates thrombin-induced microglial activation. J Biol Chem 2003, 278:31177-83.
• [42]Tammen H, Schulte I, Hess R, Menzel C, Kellmann M, Mohring T, et al.: Peptidomic analysis of human blood specimens: comparison between plasma specimens and serum by differential peptide display. Proteomics 2005, 5:3414-22.
• [43]Armstrong RC: Isolation and characterization of immature oligodendrocyte lineage cells. Methods 1998, 16:282-92.
• [44]Perizzolo KE, Sullivan S, Waugh DF: Effects of calcium binding and of EDTA and CaEDTA on the clotting of bovine fibrinogen by thrombin. Arch Biochem Biophys 1985, 237:520-34.
• [45]Piccione G, Casella S, Giannetto C, Giudice E: Effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration on canine plasma samples. J Vet Sci 2010, 11:121-4.