Temporal immune profiling in the cerebrospinal fluid and blood of patients with aneurysmal subarachnoid hemorrhage

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. 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. PB mononuclear cells (PBMCs) were collected, and their cytokine production quantified following stimulation. Mixed-effects models reveal distinct immune cell dynamics in CSF compared with blood. Monocyte/macrophage numbers continue to increase in both CSF and PBMCs for days post-aSAH. CD4⁺ human leukocyte antigen II+ T cells and CD8⁺ CD154⁺ T cells increased in circulation over time. Unstimulated PBMCs showed increased interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha production, peaking at 7 d 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 d postinjury, preceding immune cell profile alterations. 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 potential 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.