Proinflammatory Cytokines in the Embolic Model of Cerebral Ischemia in Rat
Abstract
Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke.
Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and β, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer’s instructions in ischemic and non- ischemic cortices.
While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -β (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals.
The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines.
1. Allahtavakoli M, Moloudi R, Arababadi MK, Shamsizadeh A, Javanmardi K. Delayed post ischemic treatment with Rosiglitazone attenuates infarct volume, neurological deficits and neutrophilia after embolic stroke in rat. Brain Res 2009;1271:121-7.
2. Bourrie B, Bribes E, Derocq JM, Vidal H, Casellas P. Sigma receptor ligands: applications in inflammation and oncology. Curr Opin Investig Drugs 2004; 5(11):1158-63.
3. Adibhatla RM, Dempsy R, Hatcher JF. Integration of cytokine biology and lipid metabolism in stroke. Front Biosci 2008; 13:1250-70.
4. Kadhim HJ, Duchateau J, Sebire G. Cytokines and brain injury: invited review. J Intensive Care Med 2008; 23(4):236-49.
5. Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke. J Neuroimmunol 2007; 184(1-2):53-68.
6. Haqqani AS, Nesic M, Preston E, Baumann E, Kelly J, Stanimirovic D. Characterization of vascular protein expression patterns in cerebral ischemia/reperfusion using laser capture microdissection and ICAT-nanoLC-MS/MS. Faseb J 2005; 19(13):1809-21.
7. Mulcahy NJ, Ross J, Rothwell NJ, Loddick SA. Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischaemia in the rat. Br J Pharmacol 2003; 140(3):471-6.
8. Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, et al. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol 2004; 4(2):2.
9. Lambertsen KL, Gregersen R, Meldgaard M, Clausen BH, Heibol EK, Ladeby R, et al. A role for interferon-gamma in focal cerebral ischemia in mice. J Neuropathol Exp Neurol 2004; 63(9):942-55.
10. Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, et al. Interleukin-10 in the brain. Crit Rev Immunol 2001; 21(5):427-49.
11. Ooboshi H, Ibayashi S, Shichita T, Kumai Y, Takada J, Ago T, et al. Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. Circulation 2005; 111(7):913-9.
12. van Exel E, Gussekloo J, de Craen AJ, Bootsma-van der Wiel A, Frolich M, Westendorp RG. Inflammation and stroke: the Leiden 85-Plus Study. Stroke 2002; 33(4):1135-8.
13. Todo K, Kitagawa K, Sasaki T, Omura-Matsuoka E, Terasaki Y, Oyama N, et al. Granulocyte-macrophage colony- stimulating factor enhances leptomeningeal collateral growth induced by common carotid artery occlusion. Stroke 2008;39(6):1875-82.
14. Dinapoli VA, Rosen CL, Nagamine T, Crocco T. Selective MCA occlusion: a precise embolic stroke model. J Neurosci Methods 2006; 154(1-2):233-8.
15. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986; 17(3):472-6.
16. Lo CJ, Lin JG, Kuo JS, Chiang SY, Chen SC, Liao ET, et al.Effect of salvia miltiorrhiza bunge on cerebral infarct in ischemia-reperfusion injured rats. Am J Chin Med 2003;31(2):191-200.
17. Muir KW, Tyrrell P, Sattar N, Warburton E. Inflammation and ischaemic stroke. Curr Opin Neurol 2007; 20(3):334-42.
18. Zheng Z, Yenari MA. Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res 2004; 26(8):884-92.
19. Allahtavakoli M, Jarrott B. Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro- inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats. Brain Res Bull 2011;85(3-4):219-24.
20. Saylor PJ, Kozak KR, Smith MR, Ancukiewicz MA, Efstathiou JA, Zietman AL, et al. Changes in Biomarkers of Inflammation and Angiogenesis During Androgen Deprivation Therapy for Prostate Cancer. Oncologist 2012;17(2):212-9.
21. Vestweber D. Lymphocyte trafficking through blood and lymphatic vessels: more than just selectins, chemokines and integrins. Eur J Immunol 2003; 33(5):1361-4.
22. Issekutz AC, Rowter D, Macmillan HF. Intravenous immunoglobulin G (IVIG) inhibits IL-1- and TNF-alpha- dependent, but not chemotactic-factor-stimulated, neutrophil transendothelial migration. Clin Immunol 2011; 141(2):187-96.
23. Rusu D, Drouin R, Pouliot Y, Gauthier S, Poubelle PE. A bovine whey protein extract stimulates human neutrophils to generate bioactive IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism. J Nutr 2009; 140(2):382-91.
24. Ferrante L, Opdal SH, Vege A, Rognum TO. IL-1 gene cluster polymorphisms and sudden infant death syndrome. Hum Immunol 2010; 71(4):402-6.
25. Kemik O, Kemik AS, Begenik H, Erdur FM, Emre H, Sumer A, et al. The relationship among acute-phase responce proteins, cytokines, and hormones in various gastrointestinal cancer types patients with cachectic. Hum Exp Toxicol 2011;31(2):117-25
26. Zakharova M, Ziegler HK. Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. J Immunol 2005; 175(8):5024-33.
Files | ||
Issue | Vol 13, No 2 (2014) | |
Section | Articles | |
Keywords | ||
Brain ischemia IFN-γ IL-1 IL-6 TNF-α |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |