PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage. Issue 4 (28th December 2020)

• Record Type: Journal Article
• Authors: Jackson, Christopher M; Choi, John; Routkevitch, Denis; Pant, Ayush; Saleh, Laura; Ye, Xiaobu; Caplan, Justin M; Huang, Judy; McDougall, Cameron G; Pardoll, Drew M; Brem, Henry; Tamargo, Rafael J; Lim, Michael
• Is Part Of: Neurosurgery. Volume 88:Issue 4(2021)
• Page Start: 855
• Page End: 863
• Publication Date: 2020-12-28
• Subjects: Subarachnoid hemorrhage -- Cerebral vasospasm -- Programmed death-1 -- Programmed death ligand-1 -- Monocyte; Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa495
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: BACKGROUND: Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options. OBJECTIVE: To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm. METHODS: Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm. RESULTS: We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm. CONCLUSION: Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.