Understanding the genetics of intracranial aneurysms: A primer

Laurent, Dimitri; Small, Coulter; Lucke‐Wold, Brandon; Dodd, William; Chalouhi, Nohra; Hu, Yin; Hosaka, Koji; Motwani, Kartik; Martínez, Melanie; Polifka, Adam; Koch, Matthew J.; Busl, Katharina M.; Maciel, Carolina B.; Hoh, Brian L.

doi:10.1016/j.clineuro.2021.107060

Cited by 9 publications

(12 citation statements)

References 114 publications

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“…OPN coated and MCP-1 coated coils elicited expression changes in several key mediators of vascular remodeling and tissue healing. The mediators of aneurysm healing involve many cytokines thought to underlie aneurysm formation, suggesting that the balance between healing and growth and rupture is dependent on time and concentration-specific expression of the different mediators 21. Our model of dual secreting coils demonstrates that MCP-1 and OPN co-localize with CD31 positive endothelial cells.…”

Section: Discussionmentioning

confidence: 80%

“…Increased MMP9 expression within the aneurysm wall has been reported following flow diversion and coil embolization using a rabbit model for saccular aneurysm 23. However, the balance between healing and recanalization is poorly understood, as MMP9 overexpression has been implicated in aneurysm formation, recanalization, and rupture 21 24–27. In a rabbit model, elevated MMP9 gene expression is associated with both increased coil packing density and aneurysmal healing 20.…”

Section: Discussionmentioning

confidence: 99%

“…NFκB is a heterodimer nuclear transcription factor that results in the upregulation of inflammatory proteins, including the activation of matrix metalloproteinase 9 (MMP9) 21. NFκB stimulation results in MMP9 activation and resultant vascular wall remodeling 22.…”

Section: Discussionmentioning

confidence: 99%

“…eNOS, also known as NOS3, enzymatically converts the amino acid L-arginine to the free radical species nitric oxide (NO) 21. MMP-dependent vascular remodeling is stimulated by NO in concert with reactive oxygen species, likely via the byproduct peroxynitrite 37–39.…”

Section: Discussionmentioning

confidence: 99%

“…At present, there are no well-validated animal intracranial aneurysm models that allow for the delivery of endovascular devices. The application of elastase to the adventitia of the extracranial carotid wall is, unfortunately, not physiologic and the role of elastase in cerebral aneurysm development is not known; although, abnormal elastin gene expression has been implicated in aneurysm development 21. Animals were sacrificed 3 weeks after coil implantation based on previous experiments which showed that maximal, stable tissue ingrowth is achieved at this time point 13.…”

Section: Discussionmentioning

confidence: 99%

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Combination release of chemokines from coated coils to target aneurysm healing

Laurent

Lucke‐Wold

Dodd

et al. 2022

J NeuroIntervent Surg

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BackgroundMonocyte chemoattractant protein 1 (MCP-1) and osteopontin (OPN) have been identified separately as key mediators of the aneurysm healing process following coil embolization in the rodent model. The ability of protein coated coils to accelerate this process is currently unknown.To create coils coated with both MCP-1 and OPN to target aneurysm healing.MethodsWe uses a polymer (poly(glycolide-co-caprolactone)) (Rao pharmaceuticals) (CG910) to test whether coils could be dual coated with active proteins with sequential reliable release. Coils were coated with poly-DL-lactic glycolic acid (PLGA), CG910, and subsequently dipped with protein OPN (inner layer for delayed release) and MCP-1 (outer layer for initial release). Release assays were used to measure protein elution from coils over time. To test in vivo feasibility, coated coils were implanted into carotid aneurysms to determine the effect on aneurysm healing.ResultsThe in vitro protein release assay demonstrated, a significant amount of OPN and MCP-1 release within 2 days. Using a 200 µg/µL solution of MCP-1 in phosphate-buffered saline, we showed that CG910 coated coils provide effective release of MCP over time. In the carotid aneurysm model, MCP-1 and OPN coated coils significantly increased tissue ingrowth (74% and 80%) compared with PLGA and CG910 coated coils alone (58% and 53%). To determine synergistic impact of dual coating, we measured ingrowth for MCP-1/OPN coils (63%) as well as overlap coefficients for NOX4 and NFκB with CD31.ConclusionsThis study demonstrates that MCP-1 and OPN coated coils are viable and may promote early aneurysm healing. Dual coated coils may have synergistic benefit given different location of protein interaction measured in vivo. Further work is warranted.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Combination release of chemokines from coated coils to target aneurysm healing

Laurent

Lucke‐Wold

Dodd

et al. 2022

J NeuroIntervent Surg

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Circulating immune cell landscape and T‐cell abnormalities in patients with moyamoya disease

Ge,

Tao,

Wang

et al. 2024

Clinical & Translational Med

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BackgroundMoyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive.MethodsIn this study, we employed a combination of single‐cell RNA sequencing (scRNA‐seq), mass cytometry and RNA‐sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age‐matched healthy controls.ResultsOur investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T‐cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA‐DR and p‐STAT3.ConclusionsOur findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T‐cell populations, including a decrease in effector T‐cells and an increase in regulatory T‐cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.

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Knowledge, attitude, practice and illness perception toward subarachnoid hemorrhage prevention and management among intracranial aneurysm patients

Liu,

Zhang,

et al. 2024

Clinical Neurology and Neurosurgery

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Understanding the genetics of intracranial aneurysms: A primer

Cited by 9 publications

References 114 publications

Combination release of chemokines from coated coils to target aneurysm healing

Combination release of chemokines from coated coils to target aneurysm healing

Circulating immune cell landscape and T‐cell abnormalities in patients with moyamoya disease

Knowledge, attitude, practice and illness perception toward subarachnoid hemorrhage prevention and management among intracranial aneurysm patients

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