Abstract
References
- Simon M, Grote A. Interleukin 6 and aneurysmal subarachnoid hemorrhage. a narrative review. Int J Mol Sci 2021; 22: 4133
- Etminan N, Chang HS, Hackenberg K, et al. Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis. JAMA Neurol 2019; 76(5): 588-97.
- Bederson JB, Connolly ES, Jr., Batjer HH, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009; 40: 994-1025
- Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 2010; 41: 2391-5
- Bakker MK, van der Spek RA, van Rheenen W, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet 2020; 52: 1303-13
- Masato Naraoka M, Matsuda N, Shimamura N, Ohkuma H. Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage. J Cerebral Blood Flow Metab 2022; 42: 186–96.
- Lucke-Wold BP, Logsdon AF, Manoranjan B, et al. Aneurysmal subarachnoid hemorrhage and neuroinflammation: a comprehensive review. Int J Mol Sci 2016; 17: 497
- Singh N, Hopkins SJ, Hulme S, et al. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid hemorrhage: a phase II randomized controlled trial. J Neuroinflamm 2014; 11: 1-8.
- Rothaug M, Becker-Pauly C, Rose-John S. The role of interleukin-6 signaling in nervous tissue. Biochimica et Biophysica Acta -Molecul Cell Res 2016; 1863: 1218-27.
- Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother 2017; 13: 1972-88.
- Deng HJ, Deji Q, Zhaba W, et al. A20 establishes negative feedback with TRAF6/NF-κB and attenuates early brain injury after experimental subarachnoid hemorrhage. Front Immunol 2021; 12: 623256.
- Dabus G, Nogueira RG. Current options for the management of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm: a comprehensive review of the literature. Interv Neurol 2013; 2: 30-51.
- Yeo N, Terrett L, Gupta AKJ, Care C. Contemporary management of aneurysmal subarachnoid hemorrhage: a literature review. J Neuroanaesthesiol Crit Care 2019; 6: 131-9
- Kaur S, Bansal Y, Kumar R, Bansal G. A panoramic review of IL-6: structure, pathophysiological roles, and inhibitors. Bioorganic Medicinal Chemistry 2020; 28: 115327.
- Le RQ, Li L, Yuan W, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. Oncologist 2018; 23: 943.
- Weil MH & Whigham H: Head-Down (Tredelenburg) Position for Treatment of Irreversible Hemorrhagic Shock: Experimental Study in Rats. Ann Surg 1965; 162: 905-9.
- Erdi F, Keskin F, Esen H, et al. Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm. Neurol Res 2016; 38: 224-31.
- Graetz D, Nagel A, Schlenk F, Sakowitz O, Vajkoczy P, Sarrafzadeh A. High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage. Neurologic Res 2010; 32: 728-35.
- Kang S, Tanaka T, Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol 2015; 27: 21-9.
- Pers Y-M, Schaub R, Constant E, et al. Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis. Joint Bone Spine 2015; 82: 25-30.
- Savvatis K, Müller I, Fröhlich M, et al. Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in experimental myocarditis. Basic Res Cardiol 2014; 109: 1-14.
- Pang Y, Tien LT, Zhu H, et al. Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats. Int J Mol Sci 2015; 16: 8635-54
- Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Ann Rev Immunol 2009; 28: 321-42
- Greenhalgh AD, Brough D, Robinson EM, Girard S, Rothwell NJ, Allan SM. Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology. Dis Models Mechanisms 2012; 5: 823-33
- Hanafy KA, Grobelny B, Fernandez L, et al. Brain interstitial fluid TNF-α after subarachnoid hemorrhage. J Neurol Sci 2010; 291: 69-73.
- Wu W, Guan Y, Zhao G, et al. Elevated IL-6 and TNF-alpha levels in cerebrospinal fluid of subarachnoid hemorrhage patients. Mol Neurobiol 2016; 53: 3277-85
- Wu CH, Tsai YC, Tsai TH, et al. Valproic acid reduces vasospasm through modulation of akt phosphorylation and attenuates neuronal apoptosis in subarachnoid hemorrhage rats. Int J Mol Sci 2021; 22: 5975.
- Croci DM, Wanderer S, Strange F, et al. Tocilizumab reduces vasospasms, neuronal celle death, and microclot formation in a rabbit model of subarachnoid hemorrhage. Transl Stroke Res 2021; 12: 894-904.
- Xu L, Wu J, Liu Y, Chen G, Ma C, Zhang H. Peroxisome proliferator activated receptor β/δ regulates cerebral vasospasm after subarachnoid hemorrhage via modulating vascular smooth muscle cells phenotypic conversion. Mol Med Rep 2021; 24: 860.
- Hasegawa Y, Suzuki H, Sozen T, Altay O, Zhang JH. Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. Early Brain Injury or Cerebral Vasospasm 2011; 110: 43-8
- Heinsberg LW, Weeks DE, Alexander SA, et al. Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage. Epigenetics Commun 2021; 1: 4.
- Fragata I, Bustamante A, Penalba A, et al. TNF-R1 correlates with cerebral perfusion and acute ischemia following subarachnoid hemorrhage. Neurocrit Care 2020; 33: 679-87.
- Wu F, Liu Z, Li G, et al. Inflammation and oxidative stress: potential targets for improving prognosis after subarachnoid hemorrhage. Front Cell Neurosci 2021; 15: 739506.
- Barry C, Turner RJ, Corrigan F, Vink R. New therapeutic approaches to subarachnoid hemorrhage. Expert Opin Investig Drugs 2012; 21: 845-59.
- Marsal Barril S, Martin-Martinez MA, Blanco-Garcia FJ, et al. Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting. Reumatol Clin (Engl Ed) 2022; 18: 567-73.
Abstract
Aim: This study aimed to evaluate the effects of tocilizumab (TCZ), a recombinant humanized, anti-human monoclonal antibody of the immunoglobulin G1k subclass, on vascular morphological changes, endothelial apoptosis, and the levels of pro-inflammatory and apoptotic cytokines, such as IL-6, tumor necrosis factor-alpha (TNF-α), caspase-3, Bcl-2 associated X-protein (BAX), and vascular endothelial growth factor (VEGF) in a rat SAH model.
Material and Method: The rats were randomly assigned (animal study) to 4 groups KONÜDAM Experimental Animal Research Center, Necmettin Erbakan University, Meram Faculty of Medicine, Konya, Turkey; 15/03/2019): (1) normal control (without SAH); (2) SAH (without treatment); (3) SAH treated with saline (SAH + Sal.); and (4) SAH treated with TCZ (SAH + Toc.). The tissues were measured using enzyme-linked immunosorbent assay (ELISA) kits. A series of brain and basilar artery sections were categorized into several subgroups for hematoxylin and eosin (H&E) staining, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.
Results: The levels of caspase, BAX, and IL-6 in the SAH + TOC group were significantly lower than in other groups. TCZ treatment significantly increased the lumen of the basilar artery compared with that in the SAH and SAH + SAL groups without treatment (p=0.002 and p=0.004 respectively). SAH increased the apoptotic index in the endothelium compared with TCZ treatment (p=0.027) groups.
Conclusion: It can be concluded that TCZ is safe and effective for treating experimental SAH. The results reveal clearly experimental evidence for the potential clinical application of TCZ in SAH patients.
Keywords
References
- Simon M, Grote A. Interleukin 6 and aneurysmal subarachnoid hemorrhage. a narrative review. Int J Mol Sci 2021; 22: 4133
- Etminan N, Chang HS, Hackenberg K, et al. Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis. JAMA Neurol 2019; 76(5): 588-97.
- Bederson JB, Connolly ES, Jr., Batjer HH, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009; 40: 994-1025
- Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 2010; 41: 2391-5
- Bakker MK, van der Spek RA, van Rheenen W, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet 2020; 52: 1303-13
- Masato Naraoka M, Matsuda N, Shimamura N, Ohkuma H. Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage. J Cerebral Blood Flow Metab 2022; 42: 186–96.
- Lucke-Wold BP, Logsdon AF, Manoranjan B, et al. Aneurysmal subarachnoid hemorrhage and neuroinflammation: a comprehensive review. Int J Mol Sci 2016; 17: 497
- Singh N, Hopkins SJ, Hulme S, et al. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid hemorrhage: a phase II randomized controlled trial. J Neuroinflamm 2014; 11: 1-8.
- Rothaug M, Becker-Pauly C, Rose-John S. The role of interleukin-6 signaling in nervous tissue. Biochimica et Biophysica Acta -Molecul Cell Res 2016; 1863: 1218-27.
- Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother 2017; 13: 1972-88.
- Deng HJ, Deji Q, Zhaba W, et al. A20 establishes negative feedback with TRAF6/NF-κB and attenuates early brain injury after experimental subarachnoid hemorrhage. Front Immunol 2021; 12: 623256.
- Dabus G, Nogueira RG. Current options for the management of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm: a comprehensive review of the literature. Interv Neurol 2013; 2: 30-51.
- Yeo N, Terrett L, Gupta AKJ, Care C. Contemporary management of aneurysmal subarachnoid hemorrhage: a literature review. J Neuroanaesthesiol Crit Care 2019; 6: 131-9
- Kaur S, Bansal Y, Kumar R, Bansal G. A panoramic review of IL-6: structure, pathophysiological roles, and inhibitors. Bioorganic Medicinal Chemistry 2020; 28: 115327.
- Le RQ, Li L, Yuan W, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. Oncologist 2018; 23: 943.
- Weil MH & Whigham H: Head-Down (Tredelenburg) Position for Treatment of Irreversible Hemorrhagic Shock: Experimental Study in Rats. Ann Surg 1965; 162: 905-9.
- Erdi F, Keskin F, Esen H, et al. Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm. Neurol Res 2016; 38: 224-31.
- Graetz D, Nagel A, Schlenk F, Sakowitz O, Vajkoczy P, Sarrafzadeh A. High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage. Neurologic Res 2010; 32: 728-35.
- Kang S, Tanaka T, Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol 2015; 27: 21-9.
- Pers Y-M, Schaub R, Constant E, et al. Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis. Joint Bone Spine 2015; 82: 25-30.
- Savvatis K, Müller I, Fröhlich M, et al. Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in experimental myocarditis. Basic Res Cardiol 2014; 109: 1-14.
- Pang Y, Tien LT, Zhu H, et al. Interleukin-1 receptor antagonist reduces neonatal lipopolysaccharide-induced long-lasting neurobehavioral deficits and dopaminergic neuronal injury in adult rats. Int J Mol Sci 2015; 16: 8635-54
- Rock KL, Latz E, Ontiveros F, Kono H. The sterile inflammatory response. Ann Rev Immunol 2009; 28: 321-42
- Greenhalgh AD, Brough D, Robinson EM, Girard S, Rothwell NJ, Allan SM. Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology. Dis Models Mechanisms 2012; 5: 823-33
- Hanafy KA, Grobelny B, Fernandez L, et al. Brain interstitial fluid TNF-α after subarachnoid hemorrhage. J Neurol Sci 2010; 291: 69-73.
- Wu W, Guan Y, Zhao G, et al. Elevated IL-6 and TNF-alpha levels in cerebrospinal fluid of subarachnoid hemorrhage patients. Mol Neurobiol 2016; 53: 3277-85
- Wu CH, Tsai YC, Tsai TH, et al. Valproic acid reduces vasospasm through modulation of akt phosphorylation and attenuates neuronal apoptosis in subarachnoid hemorrhage rats. Int J Mol Sci 2021; 22: 5975.
- Croci DM, Wanderer S, Strange F, et al. Tocilizumab reduces vasospasms, neuronal celle death, and microclot formation in a rabbit model of subarachnoid hemorrhage. Transl Stroke Res 2021; 12: 894-904.
- Xu L, Wu J, Liu Y, Chen G, Ma C, Zhang H. Peroxisome proliferator activated receptor β/δ regulates cerebral vasospasm after subarachnoid hemorrhage via modulating vascular smooth muscle cells phenotypic conversion. Mol Med Rep 2021; 24: 860.
- Hasegawa Y, Suzuki H, Sozen T, Altay O, Zhang JH. Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. Early Brain Injury or Cerebral Vasospasm 2011; 110: 43-8
- Heinsberg LW, Weeks DE, Alexander SA, et al. Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage. Epigenetics Commun 2021; 1: 4.
- Fragata I, Bustamante A, Penalba A, et al. TNF-R1 correlates with cerebral perfusion and acute ischemia following subarachnoid hemorrhage. Neurocrit Care 2020; 33: 679-87.
- Wu F, Liu Z, Li G, et al. Inflammation and oxidative stress: potential targets for improving prognosis after subarachnoid hemorrhage. Front Cell Neurosci 2021; 15: 739506.
- Barry C, Turner RJ, Corrigan F, Vink R. New therapeutic approaches to subarachnoid hemorrhage. Expert Opin Investig Drugs 2012; 21: 845-59.
- Marsal Barril S, Martin-Martinez MA, Blanco-Garcia FJ, et al. Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting. Reumatol Clin (Engl Ed) 2022; 18: 567-73.
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| Primary Language | English |
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| Subjects | Health Care Administration |
| Journal Section | Original Article |
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| Publication Date | May 31, 2023 |
| Published in Issue | Year 2023 Volume: 6 Issue: 3 |
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