• Christopher M Jackson, John Choi, Denis Routkevitch, Ayush Pant, Laura Saleh, Xiaobu Ye, Justin M Caplan, Judy Huang, Cameron G McDougall, Drew M Pardoll, Henry Brem, Rafael J Tamargo, and Michael Lim.
• Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
• Neurosurgery. 2021 Mar 15; 88 (4): 855-863.

BackgroundCerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options.ObjectiveTo evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm.MethodsEndovascular 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.ResultsWe 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.ConclusionOur results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.© Congress of Neurological Surgeons 2020.

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