Impaired progression of cerebral aneurysms in interleukin-1β-deficient mice

• Published in: Stroke (1970) 2006-03, Vol.37 (3), p.900-905
• Main Authors: MORIWAKI, Takuya, TAKAGI, Yasushi, SADAMASA, Nobutake, AOKI, Tomohiro, NOZAKI, Kazuhiko, HASHIMOTO, Nobuo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Diseases of the nervous system; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000204028.39783.d9

Background and Purpose— Subarachnoid hemorrhage caused by cerebral aneurysm rupture remains a life-threatening emergency despite advances in treatment. However, the mechanisms underlying aneurysm initiation, progression, and rupture remain unclear. We developed a method to induce experimental cerebral aneurysms in rats, monkeys, and mice. Interleukin-1β (IL-1β) is a key inflammatory mediator, and it is thought to be a promising target for the treatment of inflammatory diseases. In the present study, we examined the role of IL-1β in cerebral aneurysm development. Methods— Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1β gene–deficient (IL-1β−/−) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically. Results— IL-1β was expressed in vascular media in mice at an early stage of aneurysmal models’ cerebral arteries. No differences were seen in the rate of aneurysm development between IL-1β−/− and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1β−/− mice, increased caspase-1 expression was seen compared with wild-type animals. Additionally, the number of apoptotic cells assessed by single-stranded DNA immunoreactivity and TUNEL was significantly reduced in IL-1β−/− mice compared with wild-type animals. Conclusions— IL-1β is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1β gene results in the reduced incidence of mature experimental cerebral aneurysms.