Immune cells subpopulations in cerebrospinal fluid and peripheral blood of patients with Aneurysmal Subarachnoid Hemorrhage

Abstract

BackgroundThere is growing evidence supporting the role of inflammation in aneurysmal subarachnoid hemorrhage (aSAH) pathophysiology and it is of great interest to elucidate which immune mechanisms are involved.Methods12 aSAH patients and 28 healthy controls were enrolled prospectively. We assessed leukocytes subpopulations and their activation status by flow cytometry in cerebrospinal fluid (CSF) and peripheral blood (PB) of SAH patients at the same time and in PB of controls.ResultsMonocytes and neutrophils were activated in CSF of aSAH patients. The percentage of CD14++CD16+ monocytes were higher in CSF than in PB of aSAH patients, and were also increased in PB of aSAH patients compared with controls. An enhanced expression of CD69 was shown in CSF neutrophils compared with PB in aSAH patients. PB of aSAH patients showed lower percentage of total lymphocytes compared with controls PB. Additionally, lymphocytes were activated in CSF and PB of aSAH patients. CD4+ and CD8+ T cells had a decreased expression on CD3 and higher levels of CD69 in CSF compared with PB in aSAH patients. Moreover, PB CD4+ and CD8+ T cells of aSAH patients were activated compared with controls. Additionally, CD28 expression was decreased on CSF T lymphocytes.ConclusionsOur data suggest an important recruitment of leukocytes to the site of injury in aSAH as well as an increased activation at this level. Overall, these results indicate that aSAH probably stimulates both the innate and adaptive immune responses.

Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage

“…42,43 Human studies have similarly shown increases in monocyte-associated genes after aneurysm rupture, 44 elevations in monocyte chemoattractant protein 1 in serum 45 and CSF 46 after SAH, and increase in activated monocytes identified by CSF and peripheral blood flow cytometry. 7 We further found that in those SAH patients with high sST2, there . Patients with aneurysmal rupture appear to have an increase in cells expressing transmembrane ST2 (tmST2) as well as the monocyte marker CD14, with subpopulations of CD16 and CD56 positive cells.…”

“…[37][38][39][40][41] Consistent with this, we found that aneurysm rupture and high levels of sST2 after rupture were associated with shifts in immune cell populations. 7 We further found that in those SAH patients with high sST2, there versus high sST2 at the early time point (defined as below or above the median value of 75ng/ml, n = 3 in each group). 42,43 Human studies have similarly shown increases in monocyte-associated genes after aneurysm rupture, 44 elevations in monocyte chemoattractant protein 1 in serum 45 and CSF 46 after SAH, and increase in activated monocytes identified by CSF and peripheral blood flow cytometry.…”

Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review

“…Recent evidence implicates neuroinflammation as a key mediator of injury expansion and behavioral deficits [ 3 , 4 ]. Peripheral immune cells are both recruited and activated in damaged tissue [ 5 ]. These cells can enter the brain parenchyma and release inflammatory cytokines [ 6 ].…”

The role of TLR4 and HO‐1 in neuroinflammation after subarachnoid hemorrhage

“…Only one preclinical study has shown neuroprotective effects of statins via upregulation of regulatory T lymphocytes in rodent SAH models (Ayer et al, 2013). Furthermore, only two clinical studies have shown proliferation of CD4+ and CD8+ T cells in CSF and peripheral blood of SAH patients (Mathiesen, Andersson, Loftenius, & Holst, 1993;Moraes et al, 2015). Due to the paucity of research, the clinical implications of the adaptive immune system in SAH remain unexplored.…”