Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.
OBJECTIVE
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-1beta (IL-1beta) 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-1beta in cerebral aneurysm development.


METHODS
Cerebral aneurysms were experimentally induced in 5-week-old male C57BL/6 mice, IL-1beta gene-deficient (IL-1beta-/-) mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were dissected and examined histologically and immunohistochemically.


RESULTS
IL-1beta 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-1beta-/- and wild-type mice, but the percentage of advanced aneurysm change was significantly larger in wild-type animals. Furthermore, in IL-1beta-/- 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-1beta-/- mice compared with wild-type animals.


CONCLUSIONS
IL-1beta is important for the progression of cerebral aneurysms in a mouse model. Disruption of the IL-1beta gene results in the reduced incidence of mature experimental cerebral aneurysms.
Moriwaki
Takuya
T
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takagi
Yasushi
Y
Sadamasa
Nobutake
N
Aoki
Tomohiro
T
Nozaki
Kazuhiko
K
Hashimoto
Nobuo
N
D000783:Aneurysm / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000096:biosynthesis; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology; D004277:DNA, Single-Stranded / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002532:Intracranial Aneurysm / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015233:Models, Statistical; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D004277:DNA, Single-Stranded; D007375:Interleukin-1; D012313:RNA; D020170:Caspase 1