Prevention Effect of Antiplatelets on Aneurysm Rupture in a Mouse Intracranial Aneurysm Model

Abstract

Background and Purpose: Subarachnoid hemorrhage (SAH) from intracranial aneurysm rupture results in significant morbidity and mortality. In the present study, we examined the effect of most widely used antiplatelet drugs, aspirin and cilostazol, on aneurysm rupture prevention using a mouse intracranial aneurysm model. Materials and Methods: Intracranial aneurysms were induced by a combination of deoxycorticosterone acetate-salt and a single injection of elastase into the cerebrospinal fluid in mice. Treatment with aspirin or cilostazol was started 1 day after aneurysm induction. Aneurysm rupture was detected by neurological symptoms and the presence of intracranial aneurysm with SAH was confirmed by post-mortem examination. Results: Aspirin (10 mg/kg) significantly reduced aneurysm rupture (control:aspirin = 80%:31%, p < 0.05) without affecting the overall incidence of aneurysm formation (60%:62%). Cilostazol (3 mg/kg, 30 mg/kg) did not reduce both rupture rate (control:3 mg/kg:30 mg/kg = 81%:67%:77%) and the overall incidence of aneurysm formation (control:3 mg/kg:30 mg/kg = 72%:71%:76%). Tail vein bleeding time prolonged significantly in both aspirin and cilostazol groups (p < 0.01). Conclusion: Aspirin prevented aneurysm rupture in a mouse intracranial aneurysm model, while cilostazol did not. Aspirin, the most frequently used drug for patients with ischemic myocardial and cerebral diseases, is also effective in preventing cerebral aneurysmal rupture.

RETRACTED ARTICLE: Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

“…IA is a rare familial form, but it is generally thought to be the result of acquired vascular injury caused by hypertension, smoking, and other traditional risk factors [3]. Endovascular coiling or microsurgical clipping have been utilized to prevent future rupture of unruptured aneurysm in patients with high risk of rupture [4]. Although significant progress has been made in IA surgical operation, poor post-operative recovery is still presented in IA patients [5].…”

Aspirin associated with decreased rate of intracranial aneurysm growth

“…16,37 Further evidence is provided by a deoxycorticosterone acetate-salt-induced hypertension and intracranial elastase injection model of IAs, for which 3 separate studies demonstrated a lower aneurysm rupture rate in mice treated with aspirin compared to controls. 8,31,38 The first study involved mPGES-1 knockout mice, 31 the second study relied on COX-1 and COX-2 inhibitor knockout models, 8 and the third study did not involve any knockout mice. 38 Hasan and colleagues 17 used data from the International Study of Unruptured Intracranial Aneurysms (ISUIA), which prospectively followed up on a cohort of patients with 1691 unruptured IAs.…”

“…8,31,38 The first study involved mPGES-1 knockout mice, 31 the second study relied on COX-1 and COX-2 inhibitor knockout models, 8 and the third study did not involve any knockout mice. 38 Hasan and colleagues 17 used data from the International Study of Unruptured Intracranial Aneurysms (ISUIA), which prospectively followed up on a cohort of patients with 1691 unruptured IAs. 42 These researchers analyzed the risk of SAH based on the frequency of aspirin use in 58 patients with ruptured IAs compared to a matched control of 213 patients.…”

Shedding the Light on the Natural History of Intracranial Aneurysms: An Updated Overview

“…COX-2 inhibitors, angiotensin receptor blockers, and mast-cell degranulation inhibitors are still under evaluation as tailored, preventive therapies to reverse the process of growth and rupture [ 102 , 103 , 104 , 105 , 106 ].…”