Departments of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ.
Stroke. 2020 Nov;51(11):3332-3339. doi: 10.1161/STROKEAHA.120.030834. Epub 2020 Oct 6.
Inflammation has emerged as a key component of the pathophysiology of intracranial aneurysms. Mast cells have been detected in human intracranial aneurysm tissues, and their presence was associated with intramural microhemorrhage and wall degeneration. We hypothesized that mast cells play a critical role in the development of aneurysmal rupture, and that mast cells can be used as a therapeutic target for the prevention of aneurysm rupture.
Intracranial aneurysms were induced in adult mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Aneurysm formation and rupture were assessed over 3 weeks. Roles of mast cells were assessed using a mast cell stabilizer (cromolyn), a mast cell activator (C48/80), and mice that are genetically lacking mature mast cells (Kit mice).
Pharmacological stabilization of mast cells with cromolyn markedly decreased the rupture rate of aneurysms (80% versus 19%, n=10 versus n =16) without affecting the aneurysm formation. The activation of mast cells with C48/80 significantly increased the rupture rate of aneurysms (25% versus 100%, n=4 versus n=5) without affecting the overall rate of aneurysm formation. Furthermore, the genetic deficiency of mast cells significantly prevented aneurysm rupture (80% versus 25%, n=10 versus n=8, wild-type versus Kit mice).
These results suggest that mast cells play a key role in promoting aneurysm rupture but not formation. Stabilizers of mast cells may have a potential therapeutic value in preventing intracranial aneurysm rupture in patients.
炎症已成为颅内动脉瘤病理生理学的一个关键组成部分。已经在人类颅内动脉瘤组织中检测到肥大细胞，并且它们的存在与壁内微出血和壁退化有关。我们假设肥大细胞在动脉瘤破裂的发展中起关键作用，并且肥大细胞可以用作预防动脉瘤破裂的治疗靶标。
使用诱导全身性高血压和单次向脑脊液中注射弹性蛋白酶的组合，在成年小鼠中诱导颅内动脉瘤。在 3 周内评估动脉瘤的形成和破裂。使用肥大细胞稳定剂（色甘酸钠）、肥大细胞激活剂（C48/80）和遗传缺乏成熟肥大细胞的小鼠（Kit 小鼠）评估肥大细胞的作用。
用色甘酸钠稳定肥大细胞可明显降低动脉瘤的破裂率（80%对 19%，n=10 对 n=16），而不影响动脉瘤的形成。用 C48/80 激活肥大细胞可显著增加动脉瘤的破裂率（25%对 100%，n=4 对 n=5），而不影响动脉瘤的总体形成率。此外，肥大细胞的基因缺失可显著防止动脉瘤破裂（80%对 25%，n=10 对 n=8，野生型对 Kit 小鼠）。
这些结果表明，肥大细胞在促进动脉瘤破裂中起关键作用，但不促进形成。肥大细胞稳定剂可能具有预防颅内动脉瘤破裂的潜在治疗价值。
