The Stress-Immune Response in Acute Hyperglycemic Stroke Stress-immune response

Main Article Content

Kerstin Bettermann, Dr. Kusum Sinha, Dr. Rashmi Kumari, Dr. Ian A Simpson, Professor

Abstract

Diabetic and hyperglycemic stroke patients have worse clinical outcome, higher mortality rates, larger infarcts, and more severe neurological disability than euglycemic individuals. The reasons for the worse outcome in diabetes are poorly understood, but may not be fully explained by hyperglycemia alone. The objective of this prospective clinical study was to explore whether there is an association between the stress-immune response and clinical outcomes in the hyperglycemic state.


Circulating immune cells including neutrophils, monocytes, B-cells and subpopulations of T-lymphocytes were measured over 96 hours post stroke in both hyperglycemic and euglycemic patients. Cortisol and C-reactive protein (CRP) were measured daily over 4 days in the acute post-stroke phase. Short- and long-term neurological outcomes were assessed by the NIH stroke scale, modified Ranking scale and discharge disposition. Discharge dispositions were captured at discharge and 90 days post stroke. Data on infection rates and all course mortality were collected during the hospital stay and at 3 months follow up.


Hyperglycemic stroke patients had worse clinical outcomes, more in-hospital infections, less favorable discharge dispositions and higher mortality rates. Hyperglycemic individuals had higher cortisol and CRP levels, higher peripheral neutrophil concentrations and suppressed lymphocyte levels compared to their euglycemic counterparts.


Our data suggests an altered stress-immune response in the hyperglycemic state following acute ischemic stroke which could contribute to the poor clinical outcome in this high risk group.


Key words Key words: Diabetes, hyperglycemia, ischemic stroke, lymphocytes, neutrophils

Keywords: Diabetes, hyperglycemia, ischemic stroke, lymphocytes, neutrophils

Article Details

How to Cite
BETTERMANN, Kerstin et al. The Stress-Immune Response in Acute Hyperglycemic Stroke. Medical Research Archives, [S.l.], v. 8, n. 4, apr. 2020. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2081>. Date accessed: 20 apr. 2024. doi: https://doi.org/10.18103/mra.v8i4.2081.
Section
Research Articles

References

1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135 (10):e146-e603.
2. Bellolio MF, Gilmore RM, Ganti L. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 2014 (1):Cd005346.
3. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87 (5):779-89.
4. Ahmad M, Graham SH. Inflammation after stroke: mechanisms and therapeutic approaches. Transl Stroke Res. 2010;1 (2):74-84.
5. Kim JY, Park J, Chang JY, Kim SH, Lee JE. Inflammation after Ischemic Stroke: The Role of Leukocytes and Glial Cells. Exp Neurobiol. 2016;25 (5):241-51.
6. Jian Z, Liu R, Zhu X, Smerin D, Zhong Y, Gu L, et al. The Involvement and Therapy Target of Immune Cells After Ischemic Stroke. Front Immunol. 2019;10:2167.
7. Pikija S, Sztriha LK, Killer-Oberpfalzer M, Weymayr F, Hecker C, Ramesmayer C, et al. Neutrophil to lymphocyte ratio predicts intracranial hemorrhage after endovascular thrombectomy in acute ischemic stroke. J Neuroinflammation. 2018;15 (1):319.
8. Gusdon AM, Gialdini G, Kone G, Baradaran H, Merkler AE, Mangat HS, et al. Neutrophil-Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral Hemorrhage. Stroke. 2017;48 (9):2589-92.
9. Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203 (5):1273-82.
10. Shukla V, Shakya AK, Perez-Pinzon MA, Dave KR. Cerebral ischemic damage in diabetes: an inflammatory perspective. J Neuroinflammation. 2017;14 (1):21.
11. Mracsko E, Liesz A, Karcher S, Zorn M, Bari F, Veltkamp R. Differential effects of sympathetic nervous system and hypothalamic-pituitary-adrenal axis on systemic immune cells after severe experimental stroke. Brain Behav Immun. 2014;41:200-9.
12. Liesz A, Ruger H, Purrucker J, Zorn M, Dalpke A, Mohlenbruch M, et al. Stress mediators and immune dysfunction in patients with acute cerebrovascular diseases. PLoS One. 2013;8 (9):e74839.
13. Kumari R, Willing LB, Patel SD, Krady JK, Zavadoski WJ, Gibbs EM, et al. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010;30 (2):352-60.
14. Won SY, Zagorcic A, Dubinski D, Quick-Weller J, Herrmann E, Seifert V, et al. Excellent accuracy of ABC/2 volume formula compared to computer-assisted volumetric analysis of subdural hematomas. PLoS One. 2018;13 (6):e0199809.
15. Mishiro K, Imai T, Sugitani S, Kitashoji A, Suzuki Y, Takagi T, et al. Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis. PLoS One. 2014;9 (8):e103818.
16. Paciaroni M, Agnelli G, Caso V, Corea F, Ageno W, Alberti A, et al. Acute hyperglycemia and early hemorrhagic transformation in ischemic stroke. Cerebrovasc Dis. 2009;28 (2):119-23.
17. Mi D, Wang P, Yang B, Pu Y, Yang Z, Liu L. Correlation of hyperglycemia with mortality after acute ischemic stroke. Ther Adv Neurol Disord. 2018;11:1756285617731686.
18. Anrather J, Iadecola C. Inflammation and Stroke: An Overview. Neurotherapeutics. 2016;13 (4):661-70.
19. Kim E, Tolhurst AT, Cho S. Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury. J Neuroinflammation. 2014;11:83.
20. Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, et al. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007;27 (11):1798-805.
21. Bajnok A, Berta L, Orban C, Tulassay T, Toldi G. Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life-a case study. J Neuroinflammation. 2018;15 (1):191.
22. Harris AK, Ergul A, Kozak A, Machado LS, Johnson MH, Fagan SC. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke. BMC Neurosci. 2005;6:49.
23. Fadini GP, Menegazzo L, Rigato M, Scattolini V, Poncina N, Bruttocao A, et al. NETosis Delays Diabetic Wound Healing in Mice and Humans. Diabetes. 2016;65 (4):1061-71.
24. Moxon-Emre I, Schlichter LC. Neutrophil depletion reduces blood-brain barrier breakdown, axon injury, and inflammation after intracerebral hemorrhage. J Neuropathol Exp Neurol. 2011;70 (3):218-35.
25. Jickling GC, Liu D, Ander BP, Stamova B, Zhan X, Sharp FR. Targeting neutrophils in ischemic stroke: translational insights from experimental studies. J Cereb Blood Flow Metab. 2015;35 (6):888-901.
26. Barry M, Bleackley RC. Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol. 2002;2 (6):401-9.
27. Martin A, Rojas S, Chamorro A, Falcon C, Bargallo N, Planas AM. Why does acute hyperglycemia worsen the outcome of transient focal cerebral ischemia? Role of corticosteroids, inflammation, and protein O-glycosylation. Stroke. 2006;37 (5):1288-95.
28. Miro-Mur F, Laredo C, Renu A, Rudilosso S, Zhao Y, Amaro S, et al. Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy. Brain Behav Immun. 2018;70:346-53.
29. Perretti M, D'Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol. 2009;9 (1):62-70.
30. Li J, Zhao X, Meng X, Lin J, Liu L, Wang C, et al. High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome: Subanalysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events Trial. Stroke. 2016;47 (8):2025-30.
31. Matsuo R, Ago T, Hata J, Wakisaka Y, Kuroda J, Kuwashiro T, et al. Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study. PLoS One. 2016;11 (6):e0156790.
32. Arevalo-Lorido JC, Carretero-Gomez J, Fernandez-Recio JM, Alvarez-Oliva A, Gutierrez-Montano C, Najarro-Diez F, et al. Lowering C-reactive protein with statins after an ischemic stroke avoids mortality and readmissions. A prospective cohort study. Ann Med. 2015;47 (3):226-32.
33. Berbudi A, Rahmadika N, Cahyadi AI, Ruslami R. Type 2 Diabetes and its Impact on the Immune System. Curr Diabetes Rev. 2019.