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Updated: Nov 24, 2025
Analysis of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage with High Frequency Transcranial Duplex Ultrasound
Published on: June 3, 2021
PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage
Christopher M Jackson1, John Choi1, Denis Routkevitch1
1Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Insights
Programmed death-1 (PD-1) targeted therapy shows promise for preventing cerebral vasospasm after aneurysm rupture. PD-1+ monocytes are key mediators, and their frequency correlates with vasospasm severity in patients.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Translational Medicine
Background:
- Cerebral vasospasm is a significant complication following aneurysm rupture, leading to high morbidity and mortality.
- Current treatment options for cerebral vasospasm are limited, necessitating novel therapeutic approaches.
Purpose of the Study:
- To investigate the role of programmed death-1 (PD-1) in the development of cerebral vasospasm.
- To evaluate the therapeutic potential of targeting the PD-1 pathway for cerebral vasospasm.
Main Methods:
- Cerebral vasospasm was induced in mice via endovascular internal carotid artery perforation (ICAp).
- Programmed death ligand-1 (PD-L1) was administered to assess its therapeutic effect on vasospasm.
- Immune cell populations, specifically PD-1 expressing cells, were analyzed using flow cytometry.
- Peripheral blood monocytes from patients with ruptured cerebral aneurysms were analyzed to correlate PD-1 expression with clinical vasospasm.
Main Results:
- Administration of PD-L1 effectively prevented cerebral vasospasm in a mouse model.
- PD-L1 treatment inhibited the infiltration of activated monocytes (Ly6c+ and CCR2+) into the brain.
- Increased frequency of PD-1+ monocytes in the peripheral blood of patients correlated with cerebral blood flow velocities and clinical vasospasm.
Conclusions:
- PD-1+ monocytes are identified as critical mediators in the pathophysiology of cerebral vasospasm.
- Targeting the PD-1 pathway, specifically through PD-1 agonism, represents a promising novel therapeutic strategy for cerebral vasospasm.
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.
