STACY - STroke And CYtokines
The aim of this study is to study inflammatory mediators, including tumor necrosis factor (TNF) and interleukin (IL)-1beta, in blood from stroke-patients, to determine whether inflammatory mediators can be used as predictors of the neurological outcome following an ischemic stroke.
Through the last two decades the global burden of stroke has been growing. Though there has been a decline in mortality rate worldwide, stroke is still the second most common cause of death globally, with around 6.2 million deaths each year. In Denmark, there are 12,000 new cases of ischemic stroke yearly. There is a need for development of new treatments, which reduce the number of patients who are affected by permanent disability.
Ischemic stroke leads to an inflammatory response, characterized by an increased production of cytokines both locally and systemically, which has an influence on the neurological outcome and size of the infarction, by modulating the tissue injury. The two most important of these inflammatory cytokines are TNF and IL-1-beta. However, the effect on the evolution of infarction of the cytokines is dependent on their availability at the site of the border-zone of infarction, the penumbra. In rodent studies, results show that TNF and IL-1-beta are released by microglial cells, the immune system of the brain, at the early phase of an experimentally induced stroke. These have shown TNF to have both a neuroprotective and neurotoxic effect. This leaves room for further clarification of the exact role of these cytokines in stroke patients, which we will pursue in this study.
We hope that we can clarify the effects of pro- and anti-inflammatory signalling molecules immediately after a stroke and in this way, figure out if one of these could be a potential ‘target' of new neuroprotective treatments. Furthermore, we expect to identify sensitive predictors of cerebral ischemia, potentially being relevant in the prognostic assessment of individual patients.
Description of the cohort
Patients are recruited at admission through the emergency room (FAM). The population includes patients over 18 years of age, who are admitted to the Department of Neurology within the study period with suspicion of ischemic stroke. Inclusion criteria are patients with cerebral infarction debuting within 48 hours before admission. Cases of transient ischemic attack (TIA) with no validated infarction or classical symptoms will also be included in a separate group. Exclusion criteria embody space-occupying processes, sinus thrombosis, pregnancy, and the inability to write and understand Danish.
Data and biological material
In this study, we wish to gather a blood sample at admission and 72 hours after debut of symptoms. Control samples will be obtained from healthy, age-matched individuals.
A CT scan of the cerebrum is also part of standard part of diagnosis within the first 24 hours of admission. These will be used for estimation of the size of the infarction, as well as data from MR scans taken within a subpopulation of the study group. Other data to be used in the study includes DAP registry and National Institute of Health Stroke Scale (NIHSS) for patients receiving thrombolysis and thrombectomy, as well as Scandinavian Stroke Score (SSS) for the severity of the stroke. Duplex scans are routinely made as assessment of carotid artery occlusion, for which data will also be included.
Three months after debut of symptoms or admission to the hospital, functional ability will be assessed, using the modified Rankin Scale (mRS).
A total of 18 ml of blood will be taken from a vein of the arm at the day of admission and again on the third day after admission. Samples are then carried to the Department of Neurobiology at the University of Southern Denmark, where it is stored until analysis. Results of the routine blood samples are also used, by gathering from patients' journals, when available.
Collaborating researchers and departments
Department of Neurology, Odense University Hospital
- Associate Professor Kate Lykke Lambertsen, Ph.D., M.Sc.
- Specialist Chief in Neurology Søren Bak, Ph.D, MD
- Medical Student Sofie Sander Høgedal
- Specialist Chief in Neurology Anne-Mette Homburg, MD
- Specialist in Neurology Charlotte Madsen, MD
- Specialist in Neurology Alex Christensen, MD
Publications associated with the project
Hansen RB, Laursen CCH, Nawaz N, Madsen JS, Nielsen HH, Kruuse C, Møller A, Degn M, Lambertsen KL. Leukocyte TNFR1 and TNFR2 Expression Contributes to the Peripheral Immune Response in Cases with Ischemic Stroke. Cells. 2021 Apr 9;10(4):861. doi: 10.3390/cells10040861. PMID: 33918875; PMCID: PMC8069317.
Nielsen HH, Soares CB, Høgedal SS, Madsen JS, Hansen RB, Christensen AA, Madsen C, Clausen BH, Frich LH, Degn M, Sibbersen C, Lambertsen KL. Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients. Front Neurol. 2020 Jun 11;11:448. doi: 10.3389/fneur.2020.00448. PMID: 32595585; PMCID: PMC7300211.