Mechanism and clinical translation of proinflammatory cytokines in ischemic stroke_West China Medical Journal

Authors：

LIU Meng ¹ , JIANG Zhixuan ² , WANG Yanan ¹ , WU Simiao ¹ ,  HE Weihong ³

1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

HE Weihong, Email: weihong.he@outlook.com

Keywords：

Ischemic stroke; proinflammatory cytokines; mechanism; clinical translation

DOI：

10.7507/1002-0179.202604022

Video：

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Abstract Full text Figures/Tables Video References Cited by

Ischemic stroke is a major cause of death and disability in adult Chinese people. Proinflammatory cytokines may exacerbate ischemic brain injury after stroke. However, preclinical studies have shown that targeted inhibition of interleukin (IL)-1β, IL-6, and/or tumor necrosis factor-α (TNF-α) alleviated ischemic brain injury. But the efficacy of these strategies has not yet been confirmed in clinical trials. Further studies are needed to investigate the effect of anti-inflammatory therapy for stroke in clinical settings. Therefore, this article focuses on classical proinflammatory cytokines including IL-1β, IL-6, and TNF-α, and summarizes their roles and mechanisms in ischemic brain injury and progress in clinical translational research.

Citation： LIU Meng, JIANG Zhixuan, WANG Yanan, WU Simiao, HE Weihong. Mechanism and clinical translation of proinflammatory cytokines in ischemic stroke. West China Medical Journal, 2026, 41(5): 833-838. doi: 10.7507/1002-0179.202604022 Copy

1.	Wu S, Liu M. Global burden of stroke: dynamic estimates to inform action. Lancet Neurol, 2024, 23(10): 952-953.
2.	Wu S, Wang Y, Liu J, et al. Stroke in China: advances in prevention and management on the path to a healthy China. Lancet Neurol. 2026, 25(4): 379-395.
3.	Thorén M, Dixit A, Escudero-Martínez I, et al. Effect of recanalization on cerebral edema in ischemic stroke treated with thrombolysis and/or endovascular therapy. Stroke, 2020, 51(1): 216-223.
4.	Qiu YM, Zhang CL, Chen AQ, et al. Immune cells in the BBB disruption after acute ischemic stroke: targets for immune therapy?. Front Immunol, 2021, 12: 678744.
5.	Ramiro L, Simats A, García-Berrocoso T, et al. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management. Ther Adv Neurol Disord, 2018, 11: 1756286418789340.
6.	Davies CA, Loddick SA, Toulmond S, et al. The progression and topographic distribution of interleukin-1beta expression after permanent middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab, 1999, 19(1): 87-98.
7.	Liberale L, Diaz-Ca?estro C, Bonetti NR, et al. Post-ischaemic administration of the murine canakinumab-surrogate antibody improves outcome in experimental stroke. Eur Heart J, 2018, 39(38): 3511-3517.
8.	Clausen BH, Wirenfeldt M, H?gedal SS, et al. Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke. Acta Neuropathol Commun, 2020, 8(1): 81.
9.	Beridze M, Sanikidze T, Shakarishvili R, et al. Selected acute phase CSF factors in ischemic stroke: findings and prognostic value. BMC Neurol, 2011, 11: 41.
10.	Sun Y, Lu CJ, Lin CH, et al. Interleukin-1beta is increased in the cerebrospinal fluid of patients with small infarcts. Eur J Neurol, 2009, 16(7): 858-863.
11.	Mazzotta G, Sarchielli P, Caso V, et al. Different cytokine levels in thrombolysis patients as predictors for clinical outcome. EurJ Neurol, 2004, 11(6): 377-381.
12.	Tuttolomondo A, Di Sciacca R, Di Raimondo D, et al. Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: relationship with TOAST subtype, outcome and infarct site. J Neuroimmunol, 2009, 215(1/2): 84-89.
13.	Licata G, Tuttolomondo A, Di Raimondo D, et al. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost, 2009, 101(5): 929-937.
14.	Fassbender K, Rossol S, Kammer T, et al. Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci, 1994, 122(2): 135-139.
15.	Shi Q, Li R, Qu Z, et al. Longitudinal change of six common inflammatory cytokines and their relationship to anxiety, depression, and cognitive impairment in acute ischemic stroke patients. Braz J Med Biol Res, 2023, 56: e13025.
16.	Chiba T, Itoh T, Tabuchi M, et al. Interleukin-1β accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats. Mediators Inflamm, 2012, 2012: 701976.
17.	Murray KN, Girard S, Holmes WM, et al. Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia. Stroke, 2014, 45(11): 3412-3419.
18.	Touzani O, Boutin H, LeFeuvre R, et al. Interleukin-1 influences ischemic brain damage in the mouse independently of the interleukin-1 type I receptor. J Neurosci, 2002, 22(1): 38-43.
19.	Loddick SA, Rothwell NJ. Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab, 1996, 16(5):932-940.
20.	Yamasaki Y, Matsuura N, Shozuhara H, et al. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke, 1995, 26(4): 676-680.
21.	McCann SK, Cramond F, Macleod MR, et al. Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: an update. Transl Stroke Res, 2016, 7(5): 395-406.
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23.	Pradillo JM, Denes A, Greenhalgh AD, et al. Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. J Cereb Blood Flow Metab, 2012, 32(9): 1810-1819.
24.	Yang GY, Mao Y, Zhou LF, et al. Attenuation of temporary focal cerebral ischemic injury in the mouse following transfection with interleukin-1 receptor antagonist. Brain Res Mol Brain Res, 1999, 72(2): 129-137.
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26.	Relton JK, Martin D, Thompson RC, et al. Peripheral administration of Interleukin-1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat. Exp Neurol, 1996, 138(2): 206-213.
27.	Xia YY, Song SW, Min Y, et al. The effects of anakinra on focal cerebral ischemic injury in rats. CNS Neurosci Ther, 2014, 20(9): 879-881.
28.	Yang GY, Liu XH, Kadoya C, et al. Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist.J Cereb Blood Flow Metab, 1998, 18(8): 840-847.
29.	Pradillo JM, Murray KN, Coutts GA, et al. Reparative effects of interleukin-1 receptor antagonist in young and aged/co-morbid rodents after cerebral ischemia. Brain Behav Immun, 2017, 61:117-126.
30.	Dripps DJ, Brandhuber BJ, Thompson RC, et al. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem, 1991, 266(16): 10331-10336.
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32.	Greenhalgh AD, Galea J, Dénes A, et al. Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics, distribution, protection. Br J Pharmacol, 2010, 160(1): 153-159.
33.	Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum, 2008, 58(8):2443-2452.
34.	Emsley HC, Smith CJ, Georgiou RF, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients.J Neurol Neurosurg Psychiatry, 2005, 76(10): 1366-1372.
35.	Smith CJ, Hulme S, Vail A, et al. SCIL-STROKE (subcutaneous interleukin-1 receptor antagonist in ischemic stroke): a randomized controlled phase 2 trial. Stroke, 2018, 49(5): 1210-1216.
36.	Becker KJ, Dankwa D, Lee R, et al. Stroke, IL-1ra, IL1RN, infection and outcome. Neurocrit Care, 2014, 21(1): 140-146.
37.	Suzuki S, Tanaka K, Nogawa S, et al. Temporal profile and cellular localization of interleukin-6 protein after focal cerebral ischemia in rats. J Cereb Blood Flow Metab, 1999, 19(11): 1256-1262.
38.	Clark WM, Rinker LG, Lessov NS, et al. Time course of IL-6 expression in experimental CNS ischemia. Neurol Res, 1999, 21(3): 287-292.
39.	Feng Q, Wang YI, Yang Y. Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia. Exp Ther Med, 2015, 9(5): 1695-1701.
40.	Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab, 1998, 18(2): 176-179.
41.	Meng C, Zhang JC, Shi RL, et al. Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis. Neuroscience, 2015, 307: 160-170.
42.	Yamashita T, Sawamoto K, Suzuki S, et al. Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons J Neurochem, 2005, 94(2): 459-468.
43.	Clark WM, Rinker LG, Lessov NS, et al. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke, 2000, 31(7): 1715-1720.
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46.	Hall C, Nguyen DT, Mendoza K, et al. Inhibition of IL-6 trans-signaling promotes post-stroke functional recovery in a sex and dose-dependent manner. J Neuroinflammation, 2025, 22(1): 52.
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48.	De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med, 2012, 367(25): 2385-2395.
49.	Miri Y, Leander K, Eriksson P, et al. Interleukin 6 trans-signalling and the risk of future cardiovascular events in men and women. Open heart, 2021, 8(2): e001694.
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1. Wu S, Liu M. Global burden of stroke: dynamic estimates to inform action. Lancet Neurol, 2024, 23(10): 952-953.
2. Wu S, Wang Y, Liu J, et al. Stroke in China: advances in prevention and management on the path to a healthy China. Lancet Neurol. 2026, 25(4): 379-395.
3. Thorén M, Dixit A, Escudero-Martínez I, et al. Effect of recanalization on cerebral edema in ischemic stroke treated with thrombolysis and/or endovascular therapy. Stroke, 2020, 51(1): 216-223.
4. Qiu YM, Zhang CL, Chen AQ, et al. Immune cells in the BBB disruption after acute ischemic stroke: targets for immune therapy?. Front Immunol, 2021, 12: 678744.
5. Ramiro L, Simats A, García-Berrocoso T, et al. Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management. Ther Adv Neurol Disord, 2018, 11: 1756286418789340.
6. Davies CA, Loddick SA, Toulmond S, et al. The progression and topographic distribution of interleukin-1beta expression after permanent middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab, 1999, 19(1): 87-98.
7. Liberale L, Diaz-Ca?estro C, Bonetti NR, et al. Post-ischaemic administration of the murine canakinumab-surrogate antibody improves outcome in experimental stroke. Eur Heart J, 2018, 39(38): 3511-3517.
8. Clausen BH, Wirenfeldt M, H?gedal SS, et al. Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke. Acta Neuropathol Commun, 2020, 8(1): 81.
9. Beridze M, Sanikidze T, Shakarishvili R, et al. Selected acute phase CSF factors in ischemic stroke: findings and prognostic value. BMC Neurol, 2011, 11: 41.
10. Sun Y, Lu CJ, Lin CH, et al. Interleukin-1beta is increased in the cerebrospinal fluid of patients with small infarcts. Eur J Neurol, 2009, 16(7): 858-863.
11. Mazzotta G, Sarchielli P, Caso V, et al. Different cytokine levels in thrombolysis patients as predictors for clinical outcome. EurJ Neurol, 2004, 11(6): 377-381.
12. Tuttolomondo A, Di Sciacca R, Di Raimondo D, et al. Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: relationship with TOAST subtype, outcome and infarct site. J Neuroimmunol, 2009, 215(1/2): 84-89.
13. Licata G, Tuttolomondo A, Di Raimondo D, et al. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost, 2009, 101(5): 929-937.
14. Fassbender K, Rossol S, Kammer T, et al. Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci, 1994, 122(2): 135-139.
15. Shi Q, Li R, Qu Z, et al. Longitudinal change of six common inflammatory cytokines and their relationship to anxiety, depression, and cognitive impairment in acute ischemic stroke patients. Braz J Med Biol Res, 2023, 56: e13025.
16. Chiba T, Itoh T, Tabuchi M, et al. Interleukin-1β accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats. Mediators Inflamm, 2012, 2012: 701976.
17. Murray KN, Girard S, Holmes WM, et al. Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia. Stroke, 2014, 45(11): 3412-3419.
18. Touzani O, Boutin H, LeFeuvre R, et al. Interleukin-1 influences ischemic brain damage in the mouse independently of the interleukin-1 type I receptor. J Neurosci, 2002, 22(1): 38-43.
19. Loddick SA, Rothwell NJ. Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab, 1996, 16(5):932-940.
20. Yamasaki Y, Matsuura N, Shozuhara H, et al. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke, 1995, 26(4): 676-680.
21. McCann SK, Cramond F, Macleod MR, et al. Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: an update. Transl Stroke Res, 2016, 7(5): 395-406.
22. Zhang DD, Jin C, Zhang YT, et al. A novel IL-1RA-PEP fusion protein alleviates blood-brain barrier disruption after ischemia-reperfusion in male rats. J Neuroinflammation, 2018, 15(1): 16.
23. Pradillo JM, Denes A, Greenhalgh AD, et al. Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. J Cereb Blood Flow Metab, 2012, 32(9): 1810-1819.
24. Yang GY, Mao Y, Zhou LF, et al. Attenuation of temporary focal cerebral ischemic injury in the mouse following transfection with interleukin-1 receptor antagonist. Brain Res Mol Brain Res, 1999, 72(2): 129-137.
25. Zhang DD, Zou MJ, Zhang YT, et al. A novel IL-1RA-PEP fusion protein with enhanced brain penetration ameliorates cerebral ischemia-reperfusion injury by inhibition of oxidative stress and neuroinflammation. Exp Neurol, 2017, 297: 1-13.
26. Relton JK, Martin D, Thompson RC, et al. Peripheral administration of Interleukin-1 receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat. Exp Neurol, 1996, 138(2): 206-213.
27. Xia YY, Song SW, Min Y, et al. The effects of anakinra on focal cerebral ischemic injury in rats. CNS Neurosci Ther, 2014, 20(9): 879-881.
28. Yang GY, Liu XH, Kadoya C, et al. Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist.J Cereb Blood Flow Metab, 1998, 18(8): 840-847.
29. Pradillo JM, Murray KN, Coutts GA, et al. Reparative effects of interleukin-1 receptor antagonist in young and aged/co-morbid rodents after cerebral ischemia. Brain Behav Immun, 2017, 61:117-126.
30. Dripps DJ, Brandhuber BJ, Thompson RC, et al. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem, 1991, 266(16): 10331-10336.
31. Sj?str?m EO, Culot M, Leickt L, et al. Transport study of interleukin-1 inhibitors using a human in vitro model of the blood-brain barrier. Brain Behav Immun Health, 2021, 16: 100307.
32. Greenhalgh AD, Galea J, Dénes A, et al. Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics, distribution, protection. Br J Pharmacol, 2010, 160(1): 153-159.
33. Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum, 2008, 58(8):2443-2452.
34. Emsley HC, Smith CJ, Georgiou RF, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients.J Neurol Neurosurg Psychiatry, 2005, 76(10): 1366-1372.
35. Smith CJ, Hulme S, Vail A, et al. SCIL-STROKE (subcutaneous interleukin-1 receptor antagonist in ischemic stroke): a randomized controlled phase 2 trial. Stroke, 2018, 49(5): 1210-1216.
36. Becker KJ, Dankwa D, Lee R, et al. Stroke, IL-1ra, IL1RN, infection and outcome. Neurocrit Care, 2014, 21(1): 140-146.
37. Suzuki S, Tanaka K, Nogawa S, et al. Temporal profile and cellular localization of interleukin-6 protein after focal cerebral ischemia in rats. J Cereb Blood Flow Metab, 1999, 19(11): 1256-1262.
38. Clark WM, Rinker LG, Lessov NS, et al. Time course of IL-6 expression in experimental CNS ischemia. Neurol Res, 1999, 21(3): 287-292.
39. Feng Q, Wang YI, Yang Y. Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia. Exp Ther Med, 2015, 9(5): 1695-1701.
40. Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab, 1998, 18(2): 176-179.
41. Meng C, Zhang JC, Shi RL, et al. Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis. Neuroscience, 2015, 307: 160-170.
42. Yamashita T, Sawamoto K, Suzuki S, et al. Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons J Neurochem, 2005, 94(2): 459-468.
43. Clark WM, Rinker LG, Lessov NS, et al. Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke, 2000, 31(7): 1715-1720.
44. Gr?nh?j MH, Clausen BH, Fenger CD, et al. Beneficial potential of intravenously administered IL-6 in improving outcome after murine experimental stroke. Brain Behav Immun, 2017, 65:296-311.
45. Suzuki S, Tanaka K, Suzuki N. Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects.J Cereb Blood Flow Metab, 2009, 29(3): 464-479.
46. Hall C, Nguyen DT, Mendoza K, et al. Inhibition of IL-6 trans-signaling promotes post-stroke functional recovery in a sex and dose-dependent manner. J Neuroinflammation, 2025, 22(1): 52.
47. Chu X, Lan J, Ma Z, et al. Effect of IL-6 receptor inhibition on infarct volume after endovascular treatment for ischaemic stroke:a phase 2, randomised, placebo-controlled trial. EBioMedicine, 2026, 125: 106167.
48. De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med, 2012, 367(25): 2385-2395.
49. Miri Y, Leander K, Eriksson P, et al. Interleukin 6 trans-signalling and the risk of future cardiovascular events in men and women. Open heart, 2021, 8(2): e001694.
50. Ziegler L, Wallén H, Aspberg S, et al. IL6 trans-signaling associates with ischemic stroke but not with atrial fibrillation. BMC Neurol, 2021, 21(1): 306.
51. Zhai QH, Futrell N, Chen FJ. Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta and IL-2 in the rat brain following middle cerebral artery occlusion. J Neurol Sci, 1997, 152(2): 119-124.
52. Liu T, Clark RK, McDonnell PC, et al. Tumor necrosis factor-alpha expression in ischemic neurons. Stroke, 1994, 25(7): 1481-1488.
53. Sairanen T, Carpén O, Karjalainen-Lindsberg ML, et al. Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke. Stroke, 2001, 32(8): 1750-1758.
54. Zaremba J, Skrobanski P, Losy J. Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct. Biomed Pharmacother, 2001, 55(5): 258-263.
55. Ferrarese C, Mascarucci P, Zoia C, et al. Increased cytokine release from peripheral blood cells after acute stroke. J Cereb Blood Flow Metab, 1999, 19(9): 1004-1009.
56. Barone FC, Arvin B, White RF, et al. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke, 1997, 28(6): 1233-1244.
57. Pettigrew LC, Kindy MS, Scheff S, et al. Focal cerebral ischemia in the TNFalpha-transgenic rat. J Neuroinflammation, 2008, 5: 47.
58. Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab, 1998, 18(1): 52-58.
59. Wang D, Zhao J, Zhang J, et al. Targeting TNF-α: the therapeutic potential of certolizumab pegol in the early period of cerebral ischemia reperfusion injury in mice. Int Immunopharmacol, 2024, 137: 112498.
60. Martin-Villalba A, Hahne M, Kleber S, et al. Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke. Cell Death Differ, 2001, 8(7): 679-686.
61. Liberale L, Bonetti NR, Puspitasari YM, et al. TNF-α antagonism rescues the effect of ageing on stroke: perspectives for targeting inflamm-ageing. Eur J Clin Invest, 2021, 51(11): e13600.
62. Hosomi N, Ban CR, Naya T, et al. Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia. J Cereb Blood Flow Metab, 2005, 25(8): 959-967.
63. Clausen BH, Degn M, Martin NA, et al. Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia. J Neuroinflammation, 2014, 11: 203.
64. Sumbria RK, Boado RJ, Pardridge WM. Brain protection from stroke with intravenous TNFα decoy receptor-Trojan horse fusion protein. J Cereb Blood Flow Metab, 2012, 32(10): 1933-1938.
65. Tobinick E. Rapid improvement of chronic stroke deficits after perispinal etanercept: three consecutive cases. CNS Drugs, 2011, 25(2): 145-155.
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West China Medical Journal

Mechanism and clinical translation of proinflammatory cytokines in ischemic stroke

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