Increased CD8 + CD161+ Cells and Adaptive Immune Response After Aneurysmal Subarachnoid Hemorrhage. (16th November 2020) - Roa, Jorge A
Abstract: INTRODUCTION: The immune response after aneurysmal subarachnoid hemorrhage (aSAH) induces inflammation in the cerebrospinal fluid (CSF). Cerebral vasospasm (VSP) is frequently observed following aSAH and contributes to neurocognitive decline. The natural history of the immune response after aSAH has not been prospectively studied in the CSF. METHODS: Peripheral blood (PB) and CSF samples from patients with aSAH were prospectively collected at different time points after aSAH: days 0–1 (acute); days 2–4 (pre-VSP); days 5–9 (VSP) and days 10+ (post-VSP). VSP was assessed with computed tomography angiography/perfusion imaging and clinical exam. TNF-α, IL-6, VEGF and MMP-9 levels were measured. Innate and adaptive immune cells were characterized by flow cytometry. Immune cell infiltration was evaluated in the wall of 2 unruptured aneurysms using confocal immunostaining. RESULTS: Thirteen patients/aneurysms were included. Mean age was 56.3 ± 14.3 years old. Five (38.5%) patients developed VSP after a mean time of 163 ± 72.8 hours (mean 6.8 days) from aSAH. Flow cytometry demonstrated decreased numbers of CD45+ cells during the acute phase in PB of aSAH patients compared with healthy controls. In CSF, NK cells (CD3-CD161+) were increased during the acute phase and progressively declined, whereas CD8 + CD161+ cells significantly increased at days 6–9 in patients with VSP. CSF microglia (CD45dimCD11b+) showed decreased numbers in the acute phase that increased over time; this progression was particularly significant in patients with VSP. Levels of VEGF and MMP-9 were consistently higher in patients who developed VSP, with the highest difference occurring at the acute phase. Confocal immunostaining confirmed presence of CD8 + CD161+ cells in the aneurysmal wall. CONCLUSION: There is active mobilization in the CSF of innate and adaptive immune cells after aSAH. Microglia activation appears to occur later on. CD8 + CD161+ cells may have an important role in the pathogenesis of intracranial aneurysms and inflammatory response after aSAH.