Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage
Year: 2024
Type: preprint
Study design: Observational Study
Abstract: Background: Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset. Methods: Twelve aSAH patients were enrolled. Leukocyte populations and cytokine levels were analyzed in cerebrospinal fluid (CSF) and peripheral blood (PB) on days 3, 5, 7, 10, and 14 post-aSAH. Peripheral blood mononuclear cells (PBMCs) were collected and their cytokine production quantified following stimulation. Results: Mixed-effects models revealed distinct immune cell dynamics in CSF compared to blood. Natural killer T cell frequency increased over time in CSF only, while monocyte/macrophage numbers increased in both CSF and PBMCs. CD4+ HLA II+ T cells increased in circulation. Unstimulated PBMCs showed increased IL-1β, IL-6, and TNFα production, peaking at 7 days post-aSAH, coinciding with typical DCI onset. Ex vivo stimulation of PBMCs showed that only IL-6 significantly changed over time. In CSF, cytokines peaked 5 days post-injury, preceding immune cell profile alterations. Conclusions: Our findings reveal a time-dependent immune response following aSAH, with distinct within-patient patterns in CSF and PB. The early CSF cytokine peak preceding immune cell changes suggests a potential mechanistic link and identifies the cytokine response as a promising therapeutic target. This cytokine surge may drive immune cell expansion and prime PBMCs for increased inflammatory activity, potentially contributing to DCI risk. Future studies should explore the importance and sources of specific cytokines in driving immune activation. These insights may inform the development of targeted immunomodulatory strategies for preventing or managing DCI in aSAH patients.
Source: medRxiv
Institution: University of Kentucky
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Cell-Specific Actions of IL-1 / IL-1R1 Signaling Following Traumatic Brain Injury, G4892748278, The Biological Mechanisms of Metformin Effects on Aging-Associated Inflammation, Biomarkers to track effective interventions that delay dementia onset in participants of the "Risk Reduction for Alzheimer's Disease (rrAD)" trial, Rethinking repair: long-term adaptive immunity supports functional recovery for stroke patients, B Cells Directly Alter Adaptive Plasticity to Support Functional Recovery After Stroke, G6697362538, Training in Translational Research in Alzheimer's and Related Dementias (TRIAD), B Cells Directly Alter Adaptive Plasticity to Support Functional Recovery After Stroke, Development of quantitative optical tools to continuously monitor cerebral autoregulation, blood flow, oxygenation and inflammation during pediatric extracorporeal life support, Kentucky Center for Clinical and Translational Science, University of Kentucky Alzheimer's Disease Research Center
OpenAlex ID: W4401687568