1. bookVolume 24 (2016): Issue 3 (September 2016)
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

Published Online: 15 Oct 2016
Volume & Issue: Volume 24 (2016) - Issue 3 (September 2016)
Page range: 307 - 317
Received: 23 Mar 2016
Accepted: 16 Jul 2016
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Background: Thioredoxin reductase (TrxR), epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

Methods: Sprague-Dawley rats divided into three groups. Rats in control group were not subjected to any of treatments and their brains were removed under anesthesia. Middle cerebral arters were exposed but not occluded for the sham-operated rats. Animals were subjected to permanent middle cerebral arter occlusion (MCAO) in MCAO-operated group. The rats were decapitated at 16 hours (h), 48 h and 96 h after sham operation and focal cerebral ischemia. TrxR activities, EGF and TNF-α levels were measured in ischemic and non-ischemic hemispheres for all groups.

Results: In group MCAO, TrxR activities were significantly low at 48 h in ischemic hemisphere in comparison to control. After the 48 h, a remarkable increase was observed at 96 h. EGF and TNF-α levels were substantially high at 96 h in group MCAO of ischemic brain.

Conclusion: TrxR activity was reduced by oxidative stress which was formed by ischemia. EGF levels increased to exhibit neurotrophic and neuroprotective effects. After ischemia, TNF-α levels increased as a response to the tissue damage. Further studies with a higher number of experimental subjects and shorter or longer periods such as from first 30 minutes up to 3 months may be more informative to show the time-dependent variations in TrxR, EGF and TNF-α in cerebral ischemic injury.

Keywords

1. McDonald RL, Stoodley M. Pathophysiology of cerebral ischemia. Neurol Med Chir. 1998 Jan; 38(1):1-11.DOI: 10.2176/nmc.38.1.10.2176/nmc.38.1Search in Google Scholar

2. Lu J, Holmgren A. The thioredoxin antioxidant system.Free Radic Biol Med. 2014 Jan;66:75-87. DOI: 10.1016/j.freeradbiomed.2013.07.036.10.1016/j.freeradbiomed.2013.07.036Search in Google Scholar

3. Korge P, Calmettes G, Weiss JN. Increased reactive oxygen species production during reductive stress: The roles of mitochondrial glutathione and thioredoxin reductases. Biochim Biophys Acta. 2015 Jun-Jul;1847(6-7):514-25. DOI: 10.1016/j. bbabio.2015.02.012.Search in Google Scholar

4. Aon-Bertolino ML, Romero JI, Galeano P, Holubiec M, Badorrey MS, Saraceno GE, et al. Thioredoxin and glutaredoxin system proteins-immunolocalization in the rat central nervous system. Biochim Biophys Acta. 2011 Jan;1810(1):93-110. DOI: 10.1016/j.bbagen.2010.06.011.10.1016/j.bbagen.2010.06.011Search in Google Scholar

5. Oliveira SLB, Pillat MM, Cheffer A, Lameu C, Schwindt TT, Ulrich H. Functions of neurotrophins and growth factors in neurogenesis and brain repair. Cytometry A. 2013 Jan;83(1)76-89. DOI: 10.1002/cyto.a.22161.10.1002/cyto.a.22161Search in Google Scholar

6. Ma XL, Liu KD, Li FC, Jiang XM, Jiang L, Li HL. Human mesenchymal stem cells increases expression of α-tubulin and angiopoietin 1 and 2 in focal cerebral ischemia and reperfusion. Curr Neurovasc Res. 2013 May;10(2):103-11. DOI: 10.2174/1567202611310020003.10.2174/1567202611310020003Search in Google Scholar

7. Abdullah Z, Rakkar K, Bath PM, Bayraktutan U. Inhibition of TNF-α protects in vitro brain barrier from ischaemic damage. Mol Cell Neurosci. 2015 Nov;69:65-79. DOI: 10.1016/j.mcn.2015.11.003.10.1016/j.mcn.2015.11.003Search in Google Scholar

8. Majid A, He YY, Gidday JM, Kaplan SS, Gonzales ER, Park TS, et al. Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse srtrains. Stroke. 2000 Nov;31(11):2707-14. DOI: 10.1161/01.STR.31.11.2707.10.1161/01.STR.31.11.2707Search in Google Scholar

9. Shichinoke H, Kuroda S, Yasuda H, Ishikawa T, Iwai M, Horiuchi M, et al. Neuroprotective effects of the free radical scavenger Edavarone (MCI-186) in mice permanent focal brain ischemia. Brain Res. 2004 Dec;1029(2):200-6. DOI: 10.1016/j.brainres. 2004.09.055.Search in Google Scholar

10. Shichinoke H, Kuroda S, Abumiya T, Ikeda J, Kobayashi T, Yoshimoto T, et al. FK506 reduces infarct volume due to permanent focal cerebral ischemia by maintaining BAD turnover and inhibiting cytochrome c release. Brain Res. 2004 Mar;1001(1-2):51-9. DOI: 10.1016/j.brainres.2003.11.054.10.1016/j.brainres.2003.11.054Search in Google Scholar

11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurements with the folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75.10.1016/S0021-9258(19)52451-6Search in Google Scholar

12. Holmgren A. Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction. J Biol Chem. 1977 Jul;252(13):4600-6.10.1016/S0021-9258(17)40204-3Search in Google Scholar

13. Tamura A, Graham DI, McCulloch J, Teasdale GM. Focal cerebral ischemia in the rat: 2. Regional cerebral blood flow determined by 14C-iodoantipyrine autoradiography foolowing middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1981; 1(1): 61-9. DOI: 10.1038/jcbfm.1981.7.10.1038/jcbfm.1981.77328139Search in Google Scholar

14. Taxin ZH, Neymotin SA, Mohan A, Lipton P, Lytton WW. Modeling molecular pathways of neuronal ischemia. Prog Mol Biol Transl Sci. 2014;123:249-75. DOI: 10.1016/B978-0-12-397897-4.00014-0. 10.1016/B978-0-12-397897-4.00014-0429132024560148Search in Google Scholar

15. Ren Y, Wei B, Song X, An N, Zhou Y, Jin X, et al. Edaravone’s free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature. Int J Neurosci. 2015;125(8):555-65. DOI: 10.3109/00207454.2014.959121.10.3109/00207454.2014.95912125171224Search in Google Scholar

16. Manzanero S, Santro T, Arumugam TV. Neuronal oxidative stress in acute ischemic stroke: Sources and contribution to cell injury. Neurochem Int. 2013 Apr;62(5):712-8. DOI: 10.1016/j.neuint.2012.11.009.10.1016/j.neuint.2012.11.00923201332Search in Google Scholar

17. Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Hüttemann M. Molecular mechanisms of ischemia-reperfusion injury in brain: Pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol. 2013 Feb;47(1):9-23. DOI: 10.1007/s12035-012-8344-z.10.1007/s12035-012-8344-z372576623011809Search in Google Scholar

18. Nagayama T, Lan J, Henshall DC, Chen, O’Horo C, Simon RP, Chen J. Induction of oxidative DNA damage in the peri-infarct region after permanent focal cerebral ischemia. J Neurochem. 2000 Oct;75(4):1716-28. DOI: 10.1046/j.1471-4159.2000.0751716.x.10.1046/j.1471-4159.2000.0751716.x10987855Search in Google Scholar

19. Liu PK, Hsu CY, Dizdaroglu M, Floyd RA, Kow YW, Karakaya A, et al. Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion. J Neurosci. 1996 Nov;16(21):6795-806.10.1523/JNEUROSCI.16-21-06795.1996Search in Google Scholar

20. Olmez I, Ozyurt H. Reactive oxygen species and ischemic cerebrovascular disease. Neurochem Int. 2012 Jan;60(2):208-12. DOI: 10.1016/j.neuint.2011.11.009.10.1016/j.neuint.2011.11.00922122807Search in Google Scholar

21. Takagi K, Kanemitsu H, Kohno M, Mitsuda K, Tomukai N, Oka H, et al. Temporal profile of the superoxide dismutase and the ascorbic acid in focal cerebral ischemia. No To Shinkei. 1991 Nov;43(11):1075-80.Search in Google Scholar

22. Sermet A, Taşdemir N, Deniz B, Atmaca M. Timedependent changes in superoxide dismutase, catalase, xanthine dehydrogenase and oxidase activities in focal cerebral ischemia. Cytobios. 2000;102(401):157-72.Search in Google Scholar

23. Mahadik SP, Makar TK, Murthy JN, Ortiz A, Wakade CG, Karpiak SE. Temporal changes in superoxide dismutase, glutathion peroxidase, and catalase levels in primary and peri-ischemic tissue. Monosialoganglioside (GM1) treatment effects.). Mol Chem Neuropathol. 1993 Jan-Feb;18(1-2):1-14. DOI: 10.1007/BF03160018.10.1007/BF031600188466585Search in Google Scholar

24. Li X, Xiao Z, Han J, Chen L, Xiao H, Ma F, et al. Promotion of neuronal differentiation of neural progenitor cells by using EGFR antibody functionalized collagen scaffolds for spinal cord injury repair. Biomaterials. 2013 Jul;34(21):5107-16. DOI: 10.1016/j.biomaterials. 2013.03.062. Search in Google Scholar

25. Hoffmann M, Schmidt M, Wels W. Activation of EGF receptor family members suppresses the cytotoxic effects of tumor necrosis factor-alpha. Cancer Immunol Immunother. 1998 Nov;47(3):167-75. DOI: 10.1007/s002620050517.10.1007/s0026200505179829842Search in Google Scholar

26. Ahnstedt H, Stenman E, Cao L, Henriksson M, Edvinsson L. Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture. Acta Physiol (Oxf). 2012 Jun;205(2):266-78. DOI: 10.1111/j.1748-1716.2011.02392.x.10.1111/j.1748-1716.2011.02392.x22145714Search in Google Scholar

27. García Del Barco-Herrera D, Martínez NS, Coro- Antich RM, Machado JM, Alba JS, Salgueiro SR, et al. Epidermal growth factor and growth hormone-releasing peptide-6: combined therapeutic approach in experimental stroke. Restor Neurol Neurosci. 2013;31(2):213-23.10.3233/RNN-12026223314006Search in Google Scholar

28. Guegan C, Ceballos-Picot I, Chevalier E, Nicole A, Onténiente B, Sola B. Reduction of ischemic damage in NGF-transgenic mice: correlation with enhancement of antioxidant enzyme activities. Neurobiol Dis. 1999 Jun;6(3):180-9. DOI: 10.1006/nbdi.1999.0240.10.1006/nbdi.1999.024010408807Search in Google Scholar

29. Larpthaveesarp A, Ferriero DM, Gonzalez FF. Growth factors for the treatment of ischemic brain injury (growth factor treatment). Brain Sci. 2015 Apr;5(2):165-77. DOI: 10.3390/brainsci5020165.10.3390/brainsci5020165449346225942688Search in Google Scholar

30. Naylor M, Bowen KK, Sailor KA, Dempsey RJ, Vemuganti R. Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus. Neurochem Int. 2005 Dec;47(8):565-72. DOI: 10.1016/j.neuint.2005.07.003.10.1016/j.neuint.2005.07.00316154234Search in Google Scholar

31. Breitling R, Hoeller D. Current challenges in quantitative modeling of epidermal growth factor signaling. FEBS Lett. 2005 Nov;579(28):6289-94. DOI: 10.1016/j.febslet.2005.10.034.10.1016/j.febslet.2005.10.03416288752Search in Google Scholar

32. Galvez-Contreras AY, Qui-ones-Hinojosa A, Gonzalez- Perez O. The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain. Front Cell Neurosci. 2013 Dec; 7:258. DOI: 10.3389/fncel.2013.00258. 10.3389/fncel.2013.00258386544724381541Search in Google Scholar

33. Tu XK, Yang WZ, Chen JP, Chen Y, Ouyang LQ, Xu YC, et al. curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats. Inflammation. 2014 Oct;37(5):1544-51. DOI: 10.1007/s10753-014-9881-6.10.1007/s10753-014-9881-624723245Search in Google Scholar

34. Tu XK, Yang WZ, Wang CH, Shi SS, Zhang YL, Chen CM, et al. Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats. Inflammation. 2010 Oct;33(5):344-52. DOI: 10.1007/s10753-010-9191-6.10.1007/s10753-010-9191-620204486Search in Google Scholar

35. Jin R, Liu L, Zhang S, Nanda A, Li G. Role of inflammation and its mediators in acute ischemic stroke. J Cardiovasc Transl Res. 2013 Oct;6(5):834-51. DOI: 10.1007/s12265-013-9508-6.10.1007/s12265-013-9508-6382961024006091Search in Google Scholar

36. Katayama Y, Inaba T, Nito C, Ueda M. Neuroprotective effects of erythromycin on ischemic injury following permanent focal cerebral ischemia in rats. Neurol Res. 2016 Mar;38(3):275-84. DOI: 10.1080/01616412.2016.1138662.10.1080/01616412.2016.1138662Search in Google Scholar

37. Chen J, Wu X, Shao B, Zhao W, Shi W, Zhang S, et al. Increased expression of TNF receptor-associated factor 6 after rat traumatic brain injury. Cell Mol Neurobiol. 2011 Mar;31(2):269-75. DOI: 10.1007/s10571-010-9617-6.10.1007/s10571-010-9617-6Search in Google Scholar

38. Liu F, Chen MR, Liu J, Zou Y, Wang TY, Zuo YX, et al. Propofol administration improves neurological function associated with inhibition of pro-inflammatory cytokines in adult rats after traumatic brain injury. Neuropeptides. 2016 Mar 24. pii: S0143-4179(16)30027-0.Search in Google Scholar

39. Fan L, Young PR, Barone FC, Feuerstein GZ, Smith DH, McIntosh TK. Experimental brain injury induces differential expression of tumor necrosis factor-α mRNA in the CNS. Mol Brain Res. 1996 Mar;36(2):287-91. DOI: 10.1016/0169-328X(95)00274-V.10.1016/0169-328X(95)00274-VSearch in Google Scholar

40. Doll DN, Rellick SL, Barr TL, Ren X, Simpkins JW. Rapid mitochondrial dysfunction mediates TNFalpha- induced neurotoxicity. J Neurochem. 2015 Feb;132(4):443-51. DOI: 10.1111/jnc.13008. 10.1111/jnc.13008445912925492727Search in Google Scholar

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