OBJECTIVE: Even though heme-induced cerebral inflammation contributes to many of the adverse sequelae seen in patients with subarachnoid hemorrhage (SAH), little is known about the mechanism; mouse models have shown a critical role for macrophages/microglia. Macrophage CD163 is a hemoglobin scavenger receptor involved in blood clearance after SAH. The authors hypothesized that the modified Fisher score is independently associated with cerebrospinal fluid (CSF) macrophage CD163 expression on postictal day 1, and that CSF macrophage CD163 expression is associated with 1-month neurological outcome. METHODS: CSF macrophages from 21 SAH and 28 unruptured aneurysm patients (control) were analyzed for CD163 expression using flow cytometry and confocal microscopy on postictal day 1. Significant associations with modified Fisher scale grades or modified Rankin Scale scores were determined using linear regression and a matched case control analysis. RESULTS: CSF macrophage CD163 expression was significantly increased in SAH patients compared with controls (p < 0.001). The modified Fisher scale (mF) grades (β = 0.407, p = 0.005) and CSF bilirubin concentrations (β = 0.311, p = 0.015) were positively and independently associated with CSF macrophage CD163 expression when the analysis was controlled for age and sex. CSF macrophages from an SAH patient with a high mF grade had increased co-localization of CD163 and glycophorin A (CD235a, an erythrocyte marker) compared with those from an SAH patient with a low mF grade. The controls had no co-localization. CSF macrophage CD163 expression (p = 0.003) was inversely associated with 1-month neurological outcome, when SAH patients were matched based on mF grade. CONCLUSIONS: This early study suggests that CSF macrophage CD163 expression, as measured by flow cytometry, may have some neuroprotective function given its inverse association with outcome and provides unique insights into the neuroinflammatory process after SAH.
OBJECTIVE: Even though heme-induced cerebral inflammation contributes to many of the adverse sequelae seen in patients with subarachnoid hemorrhage (SAH), little is known about the mechanism; mouse models have shown a critical role for macrophages/microglia. Macrophage CD163 is a hemoglobin scavenger receptor involved in blood clearance after SAH. The authors hypothesized that the modified Fisher score is independently associated with cerebrospinal fluid (CSF) macrophage CD163 expression on postictal day 1, and that CSF macrophage CD163 expression is associated with 1-month neurological outcome. METHODS: CSF macrophages from 21 SAH and 28 unruptured aneurysmpatients (control) were analyzed for CD163 expression using flow cytometry and confocal microscopy on postictal day 1. Significant associations with modified Fisher scale grades or modified Rankin Scale scores were determined using linear regression and a matched case control analysis. RESULTS: CSF macrophage CD163 expression was significantly increased in SAHpatients compared with controls (p < 0.001). The modified Fisher scale (mF) grades (β = 0.407, p = 0.005) and CSF bilirubin concentrations (β = 0.311, p = 0.015) were positively and independently associated with CSF macrophage CD163 expression when the analysis was controlled for age and sex. CSF macrophages from an SAHpatient with a high mF grade had increased co-localization of CD163 and glycophorin A (CD235a, an erythrocyte marker) compared with those from an SAHpatient with a low mF grade. The controls had no co-localization. CSF macrophage CD163 expression (p = 0.003) was inversely associated with 1-month neurological outcome, when SAHpatients were matched based on mF grade. CONCLUSIONS: This early study suggests that CSF macrophage CD163 expression, as measured by flow cytometry, may have some neuroprotective function given its inverse association with outcome and provides unique insights into the neuroinflammatory process after SAH.
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Keywords:
BIDMC = Beth Israel Deaconess Medical Center; BSA = bovine serum albumin; CD163; CD163 = cluster of differentiation 163; CSF = cerebrospinal fluid; CT = computed tomography; DCI = delayed cerebral ischemia; EVD = external ventriculostomy drain; HO = heme oxygenase; Hb = hemoglobin; Hp = haptoglobin; ICH = intracerebral hemorrhage; IQR = interquartile range; LAR = legally authorized representative; PBS = phosphate-buffered saline; SAH = subarachnoid hemorrhage; aneurysm; mF = modified Fisher scale; mRS = modified Rankin Scale; macrophage; neuro-ICU = neurological intensive care unit; outcome; sCD163 = soluble form of CD163; subarachnoid hemorrhage; vascular disorders
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