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Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
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Mast Cell Promotes the Development of Intracranial Aneurysm Rupture
Hajime Furukawa1, Kosuke Wada1, Yoshiteru Tada1
1Departments of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Stroke
|October 6, 2020
Summary
Mast cells promote intracranial aneurysm rupture but not formation. Stabilizing mast cells may offer a therapeutic strategy to prevent aneurysm rupture in patients.
Area of Science:
- Neuroscience
- Immunology
- Cardiovascular Research
Background:
- Inflammation is crucial in intracranial aneurysm (IA) development.
- Mast cells are present in IA tissues, linked to microhemorrhage and wall degeneration.
- Mast cells are hypothesized to drive IA rupture and serve as a therapeutic target.
Purpose of the Study:
- To investigate the role of mast cells in intracranial aneurysm rupture.
- To evaluate mast cells as a potential therapeutic target for preventing IA rupture.
Main Methods:
- Intracranial aneurysms induced in mice via hypertension and elastase.
- Mast cell activity modulated using a stabilizer (cromolyn) and activator (C48/80).
- Role of mast cells assessed in genetically mast cell-deficient (KitW-sh/W-sh) mice.
Main Results:
- Cromolyn significantly reduced aneurysm rupture rates (19% vs. 80%).
- Mast cell activation with C48/80 increased rupture rates (100% vs. 25%).
- Genetic deficiency of mast cells markedly prevented aneurysm rupture (25% vs. 80% in wild-type).
Conclusions:
- Mast cells are key drivers of intracranial aneurysm rupture, not formation.
- Mast cell stabilizers show therapeutic potential for preventing IA rupture.
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