Macrophage CD163 expression is neuroprotective in subarachnoid hemorrhage patients

BACKGROUND: Subarachnoid Hemorrhage (SAH) accounts for 3-5% of total stroke patients annually. Despite its rare incidence, SAH carries a 50% mortality rate. Survivors are often left with varying degrees of disability, many will never return to their previous jobs and require long-term care. One of the leading causes for this high mortality and morbidity rate in SAH is Delay Cerebral Ischemia (DCI). Researchers are now beginning to investigate neuroinflammation as the underlying cause for DCI. Studies have shown the activation of the innate immune system in the central nervous system is initiated by excess hemoglobin in the subarachnoid space. This process is mediated by the Toll-Like Receptor 4 expressed on the tissue-resident macrophages. Activated macrophages release pro-inflammatory cytokines and cause neuronal apoptosis in the surrounding tissue. However, macrophages may also mediate neuroprotection in SAH. A macrophage surface receptor called CD163 is responsible for the recognition and endocytosis of excess hemoglobin. The thesis provides a closer assessment of the neuroprotective role of macrophages in SAH patients. METHODS: Cerebrospinal fluid (CSF) was obtained from twenty three patients diagnosed with SAH (on day 1 and day 7 post-admission) or unruptured aneurysms. Immune cells were separated from CSF and analyzed by flow cytometry. The following antibody panel was used in this study: PE-anti-CD163, PeCy7-anti-CD15, and APC-anti-CD14. Macrophage expression of CD14 and CD163 was quantified using FlowJo. SAH patients were graded by the Hunt and Hess scale for the clinical states upon admission; modified Fisher scale for the size of the hemorrhage; and modified Rankin scale for clinical outcome at the time of discharge. RESULTS: Significant increase in macrophage CD14 and CD163 expression is observed in day 1 SAH patients (p<0.05) as compared to the control group. Male SAH patients have equivocal macrophages CD163 expression on day 1 as compared to the control group (p>0.05), and significantly ...