PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage. Neurosurgery Jackson, C. M., Choi, J. n., Routkevitch, D. n., Pant, A. n., Saleh, L. n., Ye, X. n., Caplan, J. M., Huang, J. n., McDougall, C. G., Pardoll, D. M., Brem, H. n., Tamargo, R. J., Lim, M. n. 2020


Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options.To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm.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.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.Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.

View details for DOI 10.1093/neuros/nyaa495

View details for PubMedID 33370819